Sorafenib was the first multikinase inhibitor to be approved for use in metastatic renal cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was reported to inhibit angiogenesis in several model...Sorafenib was the first multikinase inhibitor to be approved for use in metastatic renal cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was reported to inhibit angiogenesis in several models. The present study was designed to assess the safety of a combination of sorafenib plus olmesartan compared to monotherapies in mice bearing Ehrlich’s ascites carcinoma cell line. Mice were divided to seven groups, 1) normal mice, 2) Ehrlich’s ascites carcinoma control, 3 - 5) olmesartan (3, 10, 30 mg/kg/day), respectively, 6) sorafenib (30 mg/kg/day) and 7) the combination group: mice received olmesartan (30 mg/kg/day) plus sorafenib. All drug treatments continued for 21 days. At the end of the experiment, a complete blood count was performed and kidney and liver functions were estimated. The combination therapy produced a non-significant change in most of the measurements of complete blood count and liver enzymes when compared to normal animals. On the other hand, the combined therapy significantly increased blood urea nitrogen when compared to normal group but did not change the serum creatinine level. Concomitant administration of olmesartan with sorafenib did not significantly augment the toxicity of the later. Therefore;olmesartan might be a safe candidate with sorafenib in treatment of cancer if clinical data proved the benefit of this combination.展开更多
Objective:To evaluate the antitumor activity of Manilkara zapota(M.zapota) L.stem bark against Ehrlich ascites carcinoma(EAC) in Swiss albino mice.Methods:The in vivo antitumour activity of the ethyl acetate extract o...Objective:To evaluate the antitumor activity of Manilkara zapota(M.zapota) L.stem bark against Ehrlich ascites carcinoma(EAC) in Swiss albino mice.Methods:The in vivo antitumour activity of the ethyl acetate extract of stem bark of M.zapota L.(EASM) was evaluated at 50,100 and 200 mg/kg bw against EAC using mean survival time.After administration of the extract of M.zapota,viable EAC cell count and body weight in the EAC tumour hosts were observed.The animal was also observed for improvement in the haematological parameters(e.g.,heamoglobin content,red and white blood cells count and differential cell count) after EASM treatment. Results:Intraperitoneal administration of EASM reduced viable EAC cells,increased the survival lime,and restored altered haematological parameters.Significant efficacy was observed for EASM at 100 mg/kg dose(P<0.05).Conclusions:It can be concluded that the elhyl acetate extract of stem bark of M.zapota L.possesses significant antitumour activity.展开更多
Objective:To investigate experimentally the possible antitumor effect of methanol extract(ME) of Calotropis gigantea L.(C.gigantean) root bark and its petroleum ether(PEF) and chloroform(CF) soluble fractions against ...Objective:To investigate experimentally the possible antitumor effect of methanol extract(ME) of Calotropis gigantea L.(C.gigantean) root bark and its petroleum ether(PEF) and chloroform(CF) soluble fractions against Ehrlich ascites carcinoma(EAC) in Swiss albino mice.Methods:The effects of ME(10 and 20 mg/kg),PEF(40 and 80 mg/kg) and CF(20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied.Hematological profile and biochemical parameters(SAI.P,SGPT and SCOT) were also estimated.Results:Results of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one.The life span of ME and CF treated animals was significandy(P【0.05) increased by 43.90%(20 mg ME/kg) and 57.07%(40 mg CF/kg).ME and CF brought back the hematological parameter more or less normal level.ME and CF also restored the altered levels of serum alkaline phosphatase(SALP) and serum glutamate oxaloacetate transaminase(SGOT).Conclusions:Methanol extract(ME) of C.gigantea root bark and its chloroform soluble fraction(CF) possesses significant antitumor activity.展开更多
Objective:To evaluate the antineoplastic activity of Eucalyptus extract(EUE) against Ehrlich ascites carcinoma(EAC)in Swiss albino mice.Methods:Preliminary examination of four plant extracts(namely Eucalyptus,Costus,A...Objective:To evaluate the antineoplastic activity of Eucalyptus extract(EUE) against Ehrlich ascites carcinoma(EAC)in Swiss albino mice.Methods:Preliminary examination of four plant extracts(namely Eucalyptus,Costus,Azadirachla.Feroniai has been done by observing the reduction ability of number of EAC cells in previously inoculated Swiss alliino mice.Among them as EuE showed maximum capability,the whole study has been conducted with EuE only. Important parameters viz.enhancement of life span,reduction of average tumor weight etc.have been studied.In addition the effects of EuE on hematological parameters in both normal and EAC inoculated mice have been measured.Effect of EuE on normal peritoneal cells has also been studied.Results:EuE reduced tumor burden remarkably.It reduced the tumor growth rate and enhanced the life span of EAC bearing mice noticeably.It reversed back the hematological parameters towards normal,reduced the Irasplanlability of EAC cells and enhanced the immunomodulatory effects in mice.The host toxic effect of EuE in mice is minimum and mostly reversible with time.All such data have been compared with those obtained by running parallel experiments with bleomycin at dose 0.3 mg/kg(i.p.).Conclusions:The Eucalyptus extract may be considered as a potent anticancer agent for advanced researches.展开更多
AIM: To investigate the chemopreventive efficacy of the Indian medicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinoma (EAC)- bearing murine model.METHODS: Male Swiss albin...AIM: To investigate the chemopreventive efficacy of the Indian medicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinoma (EAC)- bearing murine model.METHODS: Male Swiss albino mice were divided into four groups: Group A was the untreated normal control; Group B was the EAC control mice group that received serial, intraperitoneal (ip) inoculations of rapidly proliferating 2 × 10^5 viable EAC cells in 0.2 mL of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract (ALE) of the plant at a dose of 2.5 mg/kg body weight by single ip injections, once daily for 10, 20 and 30 consecutive days following tumour inoculation (ALE control); and Group D was the EAC + ALE- treatment group. The chemopreventive potential of the ALE was evaluated in a murine model by studying various biological parameters and genotoxic markers, such as tumour cell count, mean survival of the animals, haematological indices, hepatocellular histology, immunohistochemical expression of liver metallothionein (MT) protein, sister-chromatid exchanges (SCEs), and DNA alterations.RESULTS: Treatment of the EAC-bearing mice with the ALE significantly (P 〈 0.001) reduced viable tumour cell count by 68.34% (228.7 × 10^6 ± 0.53) when compared to EAC control mice (72.4 × 10^6 ± 0.49), and restored body and organ weights almost to the normal values. ALE administration also increased (P 〈 0.001) mean survival of the hosts from 35 ± 3.46 d in EAC control mice to 83 ± 2.69 d in EAC + ALE-treated mice. Haematological indices also showed marked improvement with administration of ALE in EAC-bearing animals. There was a significant increase in RBC count (P 〈 0.001), hemoglobin percent (P 〈 0.001), and haematocrit value (P 〈 0.001) from 4.3 ± 0.12, 6.4 ± 0.93, and 17.63 ± 0.72 respectively in EAC control mice to 7.1 ± 0.13, 12.1 ± 0.77, and 30.23 ± 0.57 respectively in EAC + ALE-treated group, along with concurrent decrement (P 〈 0.001) in WBC count from 18.8 ± 0.54 in EAC control to 8.4 ± 0.71 in EAC + ALE. Furthermore, treatment with ALE substantially improved hepatocellular architecture and no noticeable neoplastic lesions or foci of cellular alteration were observed. Daily administration of the ALE was found to limit liver MT expression, an important marker of cell proliferation with concomitant reduction in MT immunoreactivity (62.25 ± 2.58 vs 86.24 ± 5.69, P 〈 0.01). ALE was also potentially effective in reducing (P 〈 0.001) the frequency of SCEs from 14.94 ± 2.14 in EAC control to 5.12 ± 1.16 in EAC + ALE-treated group. Finally, in comparison to the EAC control, ALE was able to suppress in vivo DNA damage by abating the generations of'tailed' DNA by 53.59% (98.65 ± 2.31 vs 45.06 ± 1.14, P 〈 0.001), and DNA single-strand breaks (SSBs) by 38.53% (3.14 ± 0.31 vs 1.93 ± 0.23, P 〈 0.01) in EAC-bearing murine liver.CONCLUSION: Our data indicate that, ALE is beneficial in restoring haematological and hepatic histological profiles and in lengthening the survival of the animals against the proliferation of ascites tumour in vivo. Finally, the chemopreventive efficacy of the ALE is manifested in limiting MT expression and in preventing DNA alterations in murine liver. The promising results of this study suggest further investigation into the chemopreventive mechanisms of the medicinal plant A. ilicifolius in vivo and in vitro.展开更多
Objective:To assess the nuclear factor-erythroid 2-related factor-2(Nrf2)modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich asci...Objective:To assess the nuclear factor-erythroid 2-related factor-2(Nrf2)modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich ascites carcinoma growth in mice.Methods:Antioxidant activity of protocatechuic acid and caffeic acid was assessed using ferric reducing antioxidant power(FRAP)and 2,2-diphenyl-1-picrylhydrazyl(DPPH).Nrf2 activation potential of phenolic compounds was tested by quantitative realtime polymerase chain reaction,and luciferase complementation reporter assays.In vivo efficacy was tested using the Ehrlich ascites carcinoma model.Results:FRAP and DPPH radical scavenging assays showed that caffeic acid and protocatechuic acid were more potent compared with cinnamic acid and benzoic acid.Luciferase complementation reporter assays identified caffeic acid and protocatechuic acid as the activators of Nrf2.Both caffeic acid and protocatechuic acid upregulated the expression of Nrf2 target genes heme oxygenase-1(HO-1),glutamate-cysteine ligase catalytic subunit(GCLC),and glutamate-cysteine ligase modifier subunit(GCLM)and the activity of NAD(P)H:quinone oxidoreductase 1(NQO1)when tested on HCT-116 cells using a cell-based assay system at 9 h.In addition,intraperitoneal administration of caffeic acid and protocatechuic acid to Ehrlich ascites carcinoma bearing mice suppressed tumor growth and angiogenesis.Conclusions:Caffeic acid and protocatechuic acid can modulate Nrf2 and inhibit Ehrlich ascites carcinoma cells.展开更多
Objective: To detect the effect of extract of Camellia Sinensis (ECS) and extract of Camellia Ptilophylla Chang (ECPC) on DNA polymerase (Pol) of Ehrlich ascites tumor cells Methods: Referring to the method of K ...Objective: To detect the effect of extract of Camellia Sinensis (ECS) and extract of Camellia Ptilophylla Chang (ECPC) on DNA polymerase (Pol) of Ehrlich ascites tumor cells Methods: Referring to the method of K Ono, Pol was extracted from Ehrlich ascites tumor cells in mice Pol α, β, and γ were separated by phosphocellulose column chromatography and were identified The effect of ECPC and ECS on Pol was studied Results: ECPC and ECS were shown to inhibit the activity of Pol α, β, and γ IC 50 values of ECS on Pol α , β, and γ were 10 2μg/ml, 9 9μg/ml and 28 9μg/ml respectively IC 50 values of ECPC on Pol α, Pol β and Pol γ were 5 6μg/ml, 15μg/ml and 14 7μg/ml respectively The modes of inhibition of ECPC on Pol α, Pol β and Pol γ were noncompetitive with respect to template DNA The Ki values of ECPC on Pol α , β, and γ were 2 68±0 12μg/ml, 2 24±0 12μg/ml , 2 56±0 18μg/ml Conclusion: ECPC and ECS were shown to have inhibitory effect on DNA polymerase of tumor cells The mode of inhibition of ECPC on Pol α, Pol β and Pol γ were noncompetitive with respect to template DNA展开更多
The anti-tumor effect of Adansonia digitata on Ehrlich ascites carcinoma cells (EAC) is still novel talk. This study is focusing on the role of the extracts of seeds and the fruit pulp of Adansonia on the antioxidants...The anti-tumor effect of Adansonia digitata on Ehrlich ascites carcinoma cells (EAC) is still novel talk. This study is focusing on the role of the extracts of seeds and the fruit pulp of Adansonia on the antioxidants activity and the molecular changes of pro-apoptic and anti-apoptic genes expression before and after the treatment of EAC cells bearing mice. Adult female BALB/C mice were used in this study;subgrouped randomly into four groups: control group (non-tumorized);EAC tumorized group, mice was i.p. inoculated with 2.5 × 106 of EAC cells;EAC+ extract of seeds group, tumorized mice was inoculated with 2.5 × 106 of EAC cells and i.p. administered with the extract of Adansonia seeds (300 mg/kg b. wt.);EAC+ fruit pulp group, tumorized mice was inoculated with 2.5 × 106 of EAC cells and i.p. administered with the extract of Adansonia fruit pulp (300 mg/kg b. wt.). The antioxidant enzymes were inhibited in EAC cells and in ascetic fluid of tumorized mice. Also the oxidative stress was increased significantly in EAC cells bearing mice. The liver was affected with the transplantation of EAC cells as reflected by the imbalance in the antioxidants and oxidants in the EAC cells bearing mice. Moreover, the molecular changes in p53 and B-cell lymphoma (Bcl-2) genes expression were recorded in EAC cells bearing mice. The extracts of adansonia have a promising role as antioxidant action due to their antioxidant effect as they ameliorate the imbalance in antioxidants and oxidants balance. The plant extract has anti-apoptosis role by restoring the P53 and Bcl-2 genes expression. Also the plant has antitumor action as they restore tumor markers levels such as α-l-fucosidase and arginase to the normal levels.展开更多
Background and objective Previous studies have demonstrated the anti-cancer effects of propolis. However, its use is limited because of its poor bioavailability. In the present study, the major objective was to improv...Background and objective Previous studies have demonstrated the anti-cancer effects of propolis. However, its use is limited because of its poor bioavailability. In the present study, the major objective was to improve propolis bioavailability using a nanosuspension formulation. The cytotoxic effect of propolis nanosuspension (PRO-NS) on the Ehrlich ascites carcinoma (EAC) in female Swiss albino mice was investigated in comparison to the free propolis. Materials and methods A propolis-loaded nanosuspension was formulated by applying solvent-antisolvent nano-precipitation technique. The prepared PRO-NS was characterized for average particle size, polydispersity index (PDI) and zeta potential. Also, the morphology of the nanosuspension particles was investigated using scanning electron microscopy (SEM). Moreover, PRO-NS cytotoxicity was tested using EAC bearing mice. The anticancer activity of Pro-NS was assessed by studying tumor volume, life span, viable and non-viable cell count, antioxidant, biochemical estimations and proliferation of EAC cells. Results The results revealed that propolis nanoparticles were relatively spherical in shape with rough surface. The tumor bearing mice treated with PRO-NS showed increased life span and inhibited tumor growth and the proliferation of EAC cells in comparison to the free propolis (p Conclusions Our results indicate that PRO-NS has a strong inhibitory activity against growth of tumors in comparison to free propolis. The anti-tumor mechanism may be mediated by preventing oxidative damage, immune-stimulation and induction of apoptosis.展开更多
Objective:To investigate in vitro antioxidant and in vivo antitumor activity of the crude methanolic extract of Aponogeton undulatus(MAU) along with its various organic fractions.Methods:Aponogeton undulatus leaves we...Objective:To investigate in vitro antioxidant and in vivo antitumor activity of the crude methanolic extract of Aponogeton undulatus(MAU) along with its various organic fractions.Methods:Aponogeton undulatus leaves were successively extracted using methanol(MAU)and then fractionated by chloroform,ethyl acetate(EAU) and water.The total antioxidant capacity,lipid peroxidation inhibition assay.1.1-diphenyl-2-picrylhydrazyl(DPPH) free radical scavenging assay and ferrous reducing power assessment were used to evaluate the antioxidant potential of the crude extract and its organic fractions.The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma(EAC) cell bearing in Swiss albino mice.Results:EAU showed the highest antioxidant capacity as(175.80±0.41)mg/g,IC_(50)value of DPPH scavenging activity was(38.84±0.02)μg/mL and also exhibited maximum lipid peroxidation inhibition activity with the IC_(50) value of(42.52±0.32)μg/mL than other fractions.The results demonstrate that reducing power of the extract was concentration dependent.In addition,EAU was administered at 50.100 and 200 mg/kg body weight respectively to EAC cell bearing mice and a significant(P<0.05)decrease in tumor volume,packed cell volume and viable cell count and also increased the life span(17.52% .42.53% and 62.05% ).Hematological profiles were restored to normal levels in MAU treated mice as compared to EAC control mice.Conclusions:The results were found to be significant and confirmed that the Aponogeton undulatus has remarkable antitumor activity with antioxidant potential.展开更多
In mixed lymphocyte-tumor all culture in vitro, the ability of thymus lymphocytes adhering to tumor cells was found to be essentially consistent with its emperipolesis index, though not synchronous. Tumor cells at dif...In mixed lymphocyte-tumor all culture in vitro, the ability of thymus lymphocytes adhering to tumor cells was found to be essentially consistent with its emperipolesis index, though not synchronous. Tumor cells at different progressive stages and in the mixed cultures with or without Con A stimulation also varied in the sensitivity to lymphocyte adhesion and emperipolesis. Tumor adhesiveness anl emperipolesis of theymus lymphocytes and their PNA-, PNA+ subgroups were shown to be different significantly from splenic lymphocytes. Thymosin exhibited certain promotive effect on lymphocyte-tumor adhesion and emperipolesis.展开更多
Objective:To evaluate the anticancer activity of the methanolic extract of Cyathula prostrata in Ehrlich ascites carcinoma(EAC)-bearing mice with methotrexate as positive control in the advanced stage of tumorigenesis...Objective:To evaluate the anticancer activity of the methanolic extract of Cyathula prostrata in Ehrlich ascites carcinoma(EAC)-bearing mice with methotrexate as positive control in the advanced stage of tumorigenesis.Methods:EAC was induced in swiss albino mice by injecting10~6 cell/mL of tumor cell suspension intraperitoneal.The methanolic extract of Cyathula prostrata effect on the tumor cell viability,DNA fragmentation and MTT assay were carried out.Results:Methanolic extract attenuated percentage increased in the cell survival lime when compared to control group.However,the effect was less than that of methotrexat.Methotrexat and the extracts reversed the tumor-induced alterations in UNA fragmentation and MTT assay.Conclusions:The present study suggests that the methanol extract of Cyathula prostrata has significant anticancer activity and that is comparable to that of methotrexate.展开更多
Aim:This study was conducted to assess the in vivo and in vitro anti-tumor effects of diallyl disulfi de(DADS)against Ehrlich ascites carcinoma(EAC)and to suggest its probable mechanism of action.Methods:EAC was induc...Aim:This study was conducted to assess the in vivo and in vitro anti-tumor effects of diallyl disulfi de(DADS)against Ehrlich ascites carcinoma(EAC)and to suggest its probable mechanism of action.Methods:EAC was induced in female mice by intraperitoneal injection of EAC-cells from stock mice.EAC-bearing mice were orally treated with 100 mg/kg body weight for 2 weeks beginning from the 1st day of EAC intraperitoneal transplantation.Cytotoxicity effects of DADS against EAC-cells in vitro were investigated at different concentrations(0,6.25,12.5,25,50,and 100μg/mL)of DADS using trypan blue exclusion assay.Results:Data from this study exhibited a signifi cant decrease in EAC-aliquot volume as well as total and alive EAC-cell number and a marked increase in dead EAC-cell number and percent in EAC-bearing mice treated with DADS as compared with EAC-bearing control.These changes were consistent with increased number of cells which exhibited phenotypic apoptotic signs marked by a decrease in the expression of anti-apoptotic protein Bcl-2,an increase of pro-apoptotic and cell cycle arrest mediator p53 and an elevation of DNA fragmenting indicator terminal deoxynucleotidyl transferase in EAC-bearing mice treated with DADS.In addition,the tumor marker sialic acid level was markedly decreased in plasma and Ehrlich ascites in EAC-bearing mice treated with DADS.In vitro,DADS also produced anti-proliferative and anti-tumor cytotoxic potentials against EAC.Conclusion:DADS may have anti-cancer effects which may be mediated via modulation of apoptosis and cell cycle arrest.展开更多
文摘Sorafenib was the first multikinase inhibitor to be approved for use in metastatic renal cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was reported to inhibit angiogenesis in several models. The present study was designed to assess the safety of a combination of sorafenib plus olmesartan compared to monotherapies in mice bearing Ehrlich’s ascites carcinoma cell line. Mice were divided to seven groups, 1) normal mice, 2) Ehrlich’s ascites carcinoma control, 3 - 5) olmesartan (3, 10, 30 mg/kg/day), respectively, 6) sorafenib (30 mg/kg/day) and 7) the combination group: mice received olmesartan (30 mg/kg/day) plus sorafenib. All drug treatments continued for 21 days. At the end of the experiment, a complete blood count was performed and kidney and liver functions were estimated. The combination therapy produced a non-significant change in most of the measurements of complete blood count and liver enzymes when compared to normal animals. On the other hand, the combined therapy significantly increased blood urea nitrogen when compared to normal group but did not change the serum creatinine level. Concomitant administration of olmesartan with sorafenib did not significantly augment the toxicity of the later. Therefore;olmesartan might be a safe candidate with sorafenib in treatment of cancer if clinical data proved the benefit of this combination.
基金Supported by Faculty of Science,Rajshahi University,Bangladesh(No.662-5/52/UGC/Science(2)/2010)
文摘Objective:To evaluate the antitumor activity of Manilkara zapota(M.zapota) L.stem bark against Ehrlich ascites carcinoma(EAC) in Swiss albino mice.Methods:The in vivo antitumour activity of the ethyl acetate extract of stem bark of M.zapota L.(EASM) was evaluated at 50,100 and 200 mg/kg bw against EAC using mean survival time.After administration of the extract of M.zapota,viable EAC cell count and body weight in the EAC tumour hosts were observed.The animal was also observed for improvement in the haematological parameters(e.g.,heamoglobin content,red and white blood cells count and differential cell count) after EASM treatment. Results:Intraperitoneal administration of EASM reduced viable EAC cells,increased the survival lime,and restored altered haematological parameters.Significant efficacy was observed for EASM at 100 mg/kg dose(P<0.05).Conclusions:It can be concluded that the elhyl acetate extract of stem bark of M.zapota L.possesses significant antitumour activity.
文摘Objective:To investigate experimentally the possible antitumor effect of methanol extract(ME) of Calotropis gigantea L.(C.gigantean) root bark and its petroleum ether(PEF) and chloroform(CF) soluble fractions against Ehrlich ascites carcinoma(EAC) in Swiss albino mice.Methods:The effects of ME(10 and 20 mg/kg),PEF(40 and 80 mg/kg) and CF(20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied.Hematological profile and biochemical parameters(SAI.P,SGPT and SCOT) were also estimated.Results:Results of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one.The life span of ME and CF treated animals was significandy(P【0.05) increased by 43.90%(20 mg ME/kg) and 57.07%(40 mg CF/kg).ME and CF brought back the hematological parameter more or less normal level.ME and CF also restored the altered levels of serum alkaline phosphatase(SALP) and serum glutamate oxaloacetate transaminase(SGOT).Conclusions:Methanol extract(ME) of C.gigantea root bark and its chloroform soluble fraction(CF) possesses significant antitumor activity.
基金Supported by University Grant Commission,Dhaka,Bangladeshfor JA Khanam(Grant No.(676)UCC/Chemistry/(10)2007-2008/3269)
文摘Objective:To evaluate the antineoplastic activity of Eucalyptus extract(EUE) against Ehrlich ascites carcinoma(EAC)in Swiss albino mice.Methods:Preliminary examination of four plant extracts(namely Eucalyptus,Costus,Azadirachla.Feroniai has been done by observing the reduction ability of number of EAC cells in previously inoculated Swiss alliino mice.Among them as EuE showed maximum capability,the whole study has been conducted with EuE only. Important parameters viz.enhancement of life span,reduction of average tumor weight etc.have been studied.In addition the effects of EuE on hematological parameters in both normal and EAC inoculated mice have been measured.Effect of EuE on normal peritoneal cells has also been studied.Results:EuE reduced tumor burden remarkably.It reduced the tumor growth rate and enhanced the life span of EAC bearing mice noticeably.It reversed back the hematological parameters towards normal,reduced the Irasplanlability of EAC cells and enhanced the immunomodulatory effects in mice.The host toxic effect of EuE in mice is minimum and mostly reversible with time.All such data have been compared with those obtained by running parallel experiments with bleomycin at dose 0.3 mg/kg(i.p.).Conclusions:The Eucalyptus extract may be considered as a potent anticancer agent for advanced researches.
基金Supported by The Council of Scientific and Industrial Research, Government of India, No. 9/96(470)2K5-EMR-I
文摘AIM: To investigate the chemopreventive efficacy of the Indian medicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinoma (EAC)- bearing murine model.METHODS: Male Swiss albino mice were divided into four groups: Group A was the untreated normal control; Group B was the EAC control mice group that received serial, intraperitoneal (ip) inoculations of rapidly proliferating 2 × 10^5 viable EAC cells in 0.2 mL of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract (ALE) of the plant at a dose of 2.5 mg/kg body weight by single ip injections, once daily for 10, 20 and 30 consecutive days following tumour inoculation (ALE control); and Group D was the EAC + ALE- treatment group. The chemopreventive potential of the ALE was evaluated in a murine model by studying various biological parameters and genotoxic markers, such as tumour cell count, mean survival of the animals, haematological indices, hepatocellular histology, immunohistochemical expression of liver metallothionein (MT) protein, sister-chromatid exchanges (SCEs), and DNA alterations.RESULTS: Treatment of the EAC-bearing mice with the ALE significantly (P 〈 0.001) reduced viable tumour cell count by 68.34% (228.7 × 10^6 ± 0.53) when compared to EAC control mice (72.4 × 10^6 ± 0.49), and restored body and organ weights almost to the normal values. ALE administration also increased (P 〈 0.001) mean survival of the hosts from 35 ± 3.46 d in EAC control mice to 83 ± 2.69 d in EAC + ALE-treated mice. Haematological indices also showed marked improvement with administration of ALE in EAC-bearing animals. There was a significant increase in RBC count (P 〈 0.001), hemoglobin percent (P 〈 0.001), and haematocrit value (P 〈 0.001) from 4.3 ± 0.12, 6.4 ± 0.93, and 17.63 ± 0.72 respectively in EAC control mice to 7.1 ± 0.13, 12.1 ± 0.77, and 30.23 ± 0.57 respectively in EAC + ALE-treated group, along with concurrent decrement (P 〈 0.001) in WBC count from 18.8 ± 0.54 in EAC control to 8.4 ± 0.71 in EAC + ALE. Furthermore, treatment with ALE substantially improved hepatocellular architecture and no noticeable neoplastic lesions or foci of cellular alteration were observed. Daily administration of the ALE was found to limit liver MT expression, an important marker of cell proliferation with concomitant reduction in MT immunoreactivity (62.25 ± 2.58 vs 86.24 ± 5.69, P 〈 0.01). ALE was also potentially effective in reducing (P 〈 0.001) the frequency of SCEs from 14.94 ± 2.14 in EAC control to 5.12 ± 1.16 in EAC + ALE-treated group. Finally, in comparison to the EAC control, ALE was able to suppress in vivo DNA damage by abating the generations of'tailed' DNA by 53.59% (98.65 ± 2.31 vs 45.06 ± 1.14, P 〈 0.001), and DNA single-strand breaks (SSBs) by 38.53% (3.14 ± 0.31 vs 1.93 ± 0.23, P 〈 0.01) in EAC-bearing murine liver.CONCLUSION: Our data indicate that, ALE is beneficial in restoring haematological and hepatic histological profiles and in lengthening the survival of the animals against the proliferation of ascites tumour in vivo. Finally, the chemopreventive efficacy of the ALE is manifested in limiting MT expression and in preventing DNA alterations in murine liver. The promising results of this study suggest further investigation into the chemopreventive mechanisms of the medicinal plant A. ilicifolius in vivo and in vitro.
文摘Objective:To assess the nuclear factor-erythroid 2-related factor-2(Nrf2)modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich ascites carcinoma growth in mice.Methods:Antioxidant activity of protocatechuic acid and caffeic acid was assessed using ferric reducing antioxidant power(FRAP)and 2,2-diphenyl-1-picrylhydrazyl(DPPH).Nrf2 activation potential of phenolic compounds was tested by quantitative realtime polymerase chain reaction,and luciferase complementation reporter assays.In vivo efficacy was tested using the Ehrlich ascites carcinoma model.Results:FRAP and DPPH radical scavenging assays showed that caffeic acid and protocatechuic acid were more potent compared with cinnamic acid and benzoic acid.Luciferase complementation reporter assays identified caffeic acid and protocatechuic acid as the activators of Nrf2.Both caffeic acid and protocatechuic acid upregulated the expression of Nrf2 target genes heme oxygenase-1(HO-1),glutamate-cysteine ligase catalytic subunit(GCLC),and glutamate-cysteine ligase modifier subunit(GCLM)and the activity of NAD(P)H:quinone oxidoreductase 1(NQO1)when tested on HCT-116 cells using a cell-based assay system at 9 h.In addition,intraperitoneal administration of caffeic acid and protocatechuic acid to Ehrlich ascites carcinoma bearing mice suppressed tumor growth and angiogenesis.Conclusions:Caffeic acid and protocatechuic acid can modulate Nrf2 and inhibit Ehrlich ascites carcinoma cells.
文摘Objective: To detect the effect of extract of Camellia Sinensis (ECS) and extract of Camellia Ptilophylla Chang (ECPC) on DNA polymerase (Pol) of Ehrlich ascites tumor cells Methods: Referring to the method of K Ono, Pol was extracted from Ehrlich ascites tumor cells in mice Pol α, β, and γ were separated by phosphocellulose column chromatography and were identified The effect of ECPC and ECS on Pol was studied Results: ECPC and ECS were shown to inhibit the activity of Pol α, β, and γ IC 50 values of ECS on Pol α , β, and γ were 10 2μg/ml, 9 9μg/ml and 28 9μg/ml respectively IC 50 values of ECPC on Pol α, Pol β and Pol γ were 5 6μg/ml, 15μg/ml and 14 7μg/ml respectively The modes of inhibition of ECPC on Pol α, Pol β and Pol γ were noncompetitive with respect to template DNA The Ki values of ECPC on Pol α , β, and γ were 2 68±0 12μg/ml, 2 24±0 12μg/ml , 2 56±0 18μg/ml Conclusion: ECPC and ECS were shown to have inhibitory effect on DNA polymerase of tumor cells The mode of inhibition of ECPC on Pol α, Pol β and Pol γ were noncompetitive with respect to template DNA
文摘The anti-tumor effect of Adansonia digitata on Ehrlich ascites carcinoma cells (EAC) is still novel talk. This study is focusing on the role of the extracts of seeds and the fruit pulp of Adansonia on the antioxidants activity and the molecular changes of pro-apoptic and anti-apoptic genes expression before and after the treatment of EAC cells bearing mice. Adult female BALB/C mice were used in this study;subgrouped randomly into four groups: control group (non-tumorized);EAC tumorized group, mice was i.p. inoculated with 2.5 × 106 of EAC cells;EAC+ extract of seeds group, tumorized mice was inoculated with 2.5 × 106 of EAC cells and i.p. administered with the extract of Adansonia seeds (300 mg/kg b. wt.);EAC+ fruit pulp group, tumorized mice was inoculated with 2.5 × 106 of EAC cells and i.p. administered with the extract of Adansonia fruit pulp (300 mg/kg b. wt.). The antioxidant enzymes were inhibited in EAC cells and in ascetic fluid of tumorized mice. Also the oxidative stress was increased significantly in EAC cells bearing mice. The liver was affected with the transplantation of EAC cells as reflected by the imbalance in the antioxidants and oxidants in the EAC cells bearing mice. Moreover, the molecular changes in p53 and B-cell lymphoma (Bcl-2) genes expression were recorded in EAC cells bearing mice. The extracts of adansonia have a promising role as antioxidant action due to their antioxidant effect as they ameliorate the imbalance in antioxidants and oxidants balance. The plant extract has anti-apoptosis role by restoring the P53 and Bcl-2 genes expression. Also the plant has antitumor action as they restore tumor markers levels such as α-l-fucosidase and arginase to the normal levels.
文摘Background and objective Previous studies have demonstrated the anti-cancer effects of propolis. However, its use is limited because of its poor bioavailability. In the present study, the major objective was to improve propolis bioavailability using a nanosuspension formulation. The cytotoxic effect of propolis nanosuspension (PRO-NS) on the Ehrlich ascites carcinoma (EAC) in female Swiss albino mice was investigated in comparison to the free propolis. Materials and methods A propolis-loaded nanosuspension was formulated by applying solvent-antisolvent nano-precipitation technique. The prepared PRO-NS was characterized for average particle size, polydispersity index (PDI) and zeta potential. Also, the morphology of the nanosuspension particles was investigated using scanning electron microscopy (SEM). Moreover, PRO-NS cytotoxicity was tested using EAC bearing mice. The anticancer activity of Pro-NS was assessed by studying tumor volume, life span, viable and non-viable cell count, antioxidant, biochemical estimations and proliferation of EAC cells. Results The results revealed that propolis nanoparticles were relatively spherical in shape with rough surface. The tumor bearing mice treated with PRO-NS showed increased life span and inhibited tumor growth and the proliferation of EAC cells in comparison to the free propolis (p Conclusions Our results indicate that PRO-NS has a strong inhibitory activity against growth of tumors in comparison to free propolis. The anti-tumor mechanism may be mediated by preventing oxidative damage, immune-stimulation and induction of apoptosis.
基金the Department of Pharmacy,Atish Dipankar University of Science & Technology.Dhaka,Bangladesh for financial support
文摘Objective:To investigate in vitro antioxidant and in vivo antitumor activity of the crude methanolic extract of Aponogeton undulatus(MAU) along with its various organic fractions.Methods:Aponogeton undulatus leaves were successively extracted using methanol(MAU)and then fractionated by chloroform,ethyl acetate(EAU) and water.The total antioxidant capacity,lipid peroxidation inhibition assay.1.1-diphenyl-2-picrylhydrazyl(DPPH) free radical scavenging assay and ferrous reducing power assessment were used to evaluate the antioxidant potential of the crude extract and its organic fractions.The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma(EAC) cell bearing in Swiss albino mice.Results:EAU showed the highest antioxidant capacity as(175.80±0.41)mg/g,IC_(50)value of DPPH scavenging activity was(38.84±0.02)μg/mL and also exhibited maximum lipid peroxidation inhibition activity with the IC_(50) value of(42.52±0.32)μg/mL than other fractions.The results demonstrate that reducing power of the extract was concentration dependent.In addition,EAU was administered at 50.100 and 200 mg/kg body weight respectively to EAC cell bearing mice and a significant(P<0.05)decrease in tumor volume,packed cell volume and viable cell count and also increased the life span(17.52% .42.53% and 62.05% ).Hematological profiles were restored to normal levels in MAU treated mice as compared to EAC control mice.Conclusions:The results were found to be significant and confirmed that the Aponogeton undulatus has remarkable antitumor activity with antioxidant potential.
文摘In mixed lymphocyte-tumor all culture in vitro, the ability of thymus lymphocytes adhering to tumor cells was found to be essentially consistent with its emperipolesis index, though not synchronous. Tumor cells at different progressive stages and in the mixed cultures with or without Con A stimulation also varied in the sensitivity to lymphocyte adhesion and emperipolesis. Tumor adhesiveness anl emperipolesis of theymus lymphocytes and their PNA-, PNA+ subgroups were shown to be different significantly from splenic lymphocytes. Thymosin exhibited certain promotive effect on lymphocyte-tumor adhesion and emperipolesis.
文摘Objective:To evaluate the anticancer activity of the methanolic extract of Cyathula prostrata in Ehrlich ascites carcinoma(EAC)-bearing mice with methotrexate as positive control in the advanced stage of tumorigenesis.Methods:EAC was induced in swiss albino mice by injecting10~6 cell/mL of tumor cell suspension intraperitoneal.The methanolic extract of Cyathula prostrata effect on the tumor cell viability,DNA fragmentation and MTT assay were carried out.Results:Methanolic extract attenuated percentage increased in the cell survival lime when compared to control group.However,the effect was less than that of methotrexat.Methotrexat and the extracts reversed the tumor-induced alterations in UNA fragmentation and MTT assay.Conclusions:The present study suggests that the methanol extract of Cyathula prostrata has significant anticancer activity and that is comparable to that of methotrexate.
文摘Aim:This study was conducted to assess the in vivo and in vitro anti-tumor effects of diallyl disulfi de(DADS)against Ehrlich ascites carcinoma(EAC)and to suggest its probable mechanism of action.Methods:EAC was induced in female mice by intraperitoneal injection of EAC-cells from stock mice.EAC-bearing mice were orally treated with 100 mg/kg body weight for 2 weeks beginning from the 1st day of EAC intraperitoneal transplantation.Cytotoxicity effects of DADS against EAC-cells in vitro were investigated at different concentrations(0,6.25,12.5,25,50,and 100μg/mL)of DADS using trypan blue exclusion assay.Results:Data from this study exhibited a signifi cant decrease in EAC-aliquot volume as well as total and alive EAC-cell number and a marked increase in dead EAC-cell number and percent in EAC-bearing mice treated with DADS as compared with EAC-bearing control.These changes were consistent with increased number of cells which exhibited phenotypic apoptotic signs marked by a decrease in the expression of anti-apoptotic protein Bcl-2,an increase of pro-apoptotic and cell cycle arrest mediator p53 and an elevation of DNA fragmenting indicator terminal deoxynucleotidyl transferase in EAC-bearing mice treated with DADS.In addition,the tumor marker sialic acid level was markedly decreased in plasma and Ehrlich ascites in EAC-bearing mice treated with DADS.In vitro,DADS also produced anti-proliferative and anti-tumor cytotoxic potentials against EAC.Conclusion:DADS may have anti-cancer effects which may be mediated via modulation of apoptosis and cell cycle arrest.