Copper complexes of anthrahydrazone bearing pyridyl side chain:Synthesis,crystal structure,anticancer activity,and DNA binding

To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.

Molecular analysis and anticancer properties of two identified isolates,Fusarium solani and Emericella nidulans isolated from Wady El-Natron soil in Egypt against Caco-2(ATCC) cell line

Objective:To characterize,identify and investigate the anticancer properties of two new soil fungal isolates,Emericella nidulansand Fusarium solani isolated from Wady El-Natron in Egypt against colon cancer Caco-2(ATCCj cell line.Methods:Soil sample was cultured and two strains were chosen for morphological and phenotypical characterization.Partial sequences of the 18s rRNA gene and the internal transcribed spacer region ITS of the two isolates were amplified by PCR.Phylogenetic tree construction and analysis of the resulted multiple sequences from the two fugal isolates were also carried out.In vitro anticancer activity of the two strains was done against colon Caco-2 cancer cell line.Reverse transcription — PCR was carried out to detect level of expression of p53 in Caco-2 cell line.Results:HF.I displayed morphological and genotypic characteristics most similar to that of Fusarium solani while HF.2 was most similar to Emericella nidulans with high similarity of 99%and 97%respectively.The multiple sequence alignment of the two fungal isolates showed that,the maximum identical conserved domains in the 18s rRNA genes were identified with the nucleotide regions of Slst to 399th base pairs,88th to 525th base pairs respectively.While those in the ITS genes were identified with the nucleotide regions of 88th to 463rd and Slst to 274th.The two isolates showed IC<sub>50 value with（6.24±5.21） and（9.84±0.36） μ g/mL) concentrations respectively at 28h.Reverse transcription- PCR indicated that these cells showed high level of expression for p53 mRNA.Conclusions:The morphology and molecular analysis identified HF.1 and HF.2 to be Fusarium solani and Emericella nidulans;new isolates of anticancer producing fungi from Wady El-Natroon city in Egypt.Treatment with the two isolates caused P53 expression in Caco-2 cell line.These two isolates can be used as an anticancer agents.

Molecular interactions between anticancer drugs and iodinated contrast media: An in vitro spectroscopic study

Purpose: The purpose of this study is to assess molecular interactions between several anticancer drugs and an iodinated contrast medium by Fourier transform infrared spectroscopy (FT-IR) and ultraviolet-visible spectroscopy (UV-Vis). Materials and Methods: Iopamidol (IPM) was used as an iodinated contrast medium, and mitomycin C (MTI), epirubicin hydrochloride (EPI), cisplatin (CDDP), 5-fluorouracil (5FU), irinotecan hydrochloride (CPT11), gemcitabine hydrochloride (dFdC), carboplatin (CBDCA), oxaliplatin (1OHP), paclitaxel hydrochloride (TAX) and docetaxel trihydrate (TXT) were used as anticancer drugs. For FT-IR, the purified IPM was mixed stoichiometrically with each anticancer drug as well as with a combination of MTI and EPI. After measuring each separated sample and the mixtures, the spectra of the mixtures were compared with the spectra of the sum of pure samples or the combination. For UV-Vis, IPM and anticancer drugs were dissolved in pure water;subsequently for the titration experiments, the mixtures were prepared by varying the molar ratio. IR absorption corresponds to stretching vibrations between atoms having covalent bonding, whereas UV-Vis spectra depend on molecular dynamics and shapes. Both UV-Vis and IR spectra change when there are molecular interactions such as aromatic ring stacking and hydrogen bonding. Result: IPM exhibited molecular interactions with MTI, EPI, CDDP, dFdC, CBDCA, 1OHP, TAX and TXT, as well as with the combination of MTI and EPI on FT-IR. However, molecular interactions were not observed on UV-Vis. Conclusion: Several anticancer drugs have molecular interactions with IPM, which could be clinically utilized for superselective intraarterial infusion chemotherapy.

Deep lingual arterial chemoembolization of tongue carcinoma with microcapsuled anticancer drug

Objective: Microcapsule chemoembolism is a promising treatment of tumors. We describe a deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum. Methods: Lingual artery cast specimens from cadavers were microscopically examined, and 78 patients with tongue cancer were recruited and treated with the deep lingual arterial embolization therapy. Results: Microcapsule embolism occurred approximately at the fifth or sixth level of the deep lingual artery branches. The five-year survival rate was 88.5% (69 out of 78), and the ten-year survival rate 52.6% (41 out of 78). Conclusion: The deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum is an effective therapy to treat carcinoma in mid-margin or mid-body of the tongue.

Granulocyte Colony-Stimulating Factor Enhances the Anticancer Effects of Cisplatin against Lung Cancer by Promoting Angiogenesis

The G-CSF is used as a therapeutic drug of the febrile neutropenia in lung cancer chemotherapy, however, there were few reports that showed the effects of combination effects of G-CSF and anticancer drugs against lung cancer. In the present study, we investigated the effects of G-CSF and the combination effects of G-CSF and cisplatin on lung cancer growth. We investigated the effect of G-CSF against the LL-2 and KLN-205 cells by MTT assay and tried to detect the G-CSF receptor by RT-PCR. Next, to analyze the G-CSF effects in vivo, we transplanted the LL-2 into C57BL/6 mice, intraperitoneally administered G-CSF (30 micro/kg/day) with or without cisplatin (5 mg/kg), measured the tumor size and analyzed pathologically by HE and immunostaining. In vitro analyses, G-CSF showed no effects in LL-2 and KLN-205 cells, and RT-PCR revealed no G-CSF receptor mRNA. In vivo analyses, G-CSF alone did not significantly suppress tumor growth. However, concurrent G-CSF administration with cisplatin significantly enhanced the tumor suppressing effect of cisplatin in early stage of tumor growth. The analysis data of vWF immunostaining indicated that the neovascularization in the peripheral region of the tumors was more enhanced in G-CSF treatment mice. ELISA assay revealed that G-CSF did not influence the serum concentration of TNF-alpha and IL-12 in tumor-bearing mice. This study suggests that concurrent (combination) administration of cisplatin with G-CSF is a safe and effective method for enhancing anticancer effects and reducing chemotherapeutic agent-induced myelosuppression.

The Anticancer Potential of Quassinoids-A Mini-Review

The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.

Synergistic anticancer effect of the extracts from Polyalthia evecta caused apoptosis in human hepatoma(HepG2)cells

Objective:To evaluate the anticancer activity of the extract fraction of Polyalthia evecta(P. evecta)(Pierre) Finet & Gagnep and the synergistic anticancer effect of the extracts from P.evecta by using the ATR/FT-IR spectroscopy.Methods:The 50%ethanol-water crude leaf extract of P.evecta(EW-L) was prepared and was further fractionated to isolate various fractions.The anticancer activity was investigated from cytotoxicity against HepG2 using a neutral red assay and apoptosis induction by evaluation of nuclei morphological changes after DAPI staining. Synergistic anticancer effects of the extracts from P.evecta were performed using the ATR/FTIR spectroscopy.Results:The result showed that the EW-L showed higher cytotoxicity and apoptosis induction in HepG2 cells than its fractionated extracts.The hexane extract exhibited higher cytotoxicity and apoptosis induction than the water extracts,but less than the EW-L. The combined water and hexane extracts apparently increased cytotoxicity and apoptosis induction.The%apoptotic cells induced by the extract mixture were increased about 2-fold compared to the single hexane extract Conclusions:The polar extract fraction is necessary for the anticancer activity of the non-polar extract fraction.The ATR/FT-IR spectra illustrates the physical interaction among the constituents in the extract mixture and reveals the presence of polyphenolic constituents in the EW-L,which might play a role for the synergistic anticancer effect.

Anticancer property of sediment actinomycetes against MCF-7 and MDA-MB-231 cell lines

ObjectiveTo investigate the anticancer property of marine sediment actinomycetes against two different breast cancer cell lines.MethodsIn vitro anticancer activity was carried out against breast (MCF-7 and MDA-MB-231) cancer cell lines. Partial sequences of the 16s rRNA gene, phylogenetic tree construction, multiple sequence analysis and secondary structure analysis were also carried out with the actinomycetes isolates.ResultsOf the selected five actinomycete isolates, ACT01 and ACT02 showed the IC50 value with (10.13±0.92) and (22.34±5.82) μg/mL concentrations, respectively for MCF-7 cell line at 48 h, but ACT01 showed the minimum (18.54±2.49 μg/mL) level of IC50 value with MDA-MB-231 cell line. Further, the 16s rRNA partial sequences of ACT01, ACT02, ACT03, ACT04 and ACT05 isolates were also deposited in NCBI data bank with the accession numbers of GQ478246, GQ478247, GQ478248, GQ478249 and GQ478250, respectively. The phylogenetic tree analysis showed that, the isolates of ACT02 and ACT03 were represented in group I and III, respectively, but ACT01 and ACT02 were represented in group II. The multiple sequence alignment of the actinomycete isolates showed that, the maximum identical conserved regions were identified with the nucleotide regions of 125 to 221st base pairs, 65 to 119th base pairs and 55, 48 and 31st base pairs. Secondary structure prediction of the 16s rRNA showed that, the maximum free energy was consumed with ACT03 isolate (-45.4 kkal/mol) and the minimum free energy was consumed with ACT04 isolate (?7.6 kkal/mol).ConclusionsThe actinomycete isolates of ACT01 and ACT02 (GQ478246 and GQ478247) which are isolated from sediment sample can be further used as anticancer agents against breast cancer cell lines.

Cytotoxicity, Toxicity and Anticancer Activity of Manuka Honey, Saudi’s Honey and Peganum harmala Plant against Cancer Cells

Cancer occurs when the body’s cells grow beyond the usual control. Normal body cells multiply in a controlled manner and undergo apoptosis when the body no longer needs them. Different types of cancers exist, and the common ones include breast, cervical, prostate, lung, colon, and skin cancers. Several factors have been associated with cancers, and these factors include poor dieting, exposure to harmful chemicals and radiation, weak immune system, and genetics. Cancer presents an enormous health threat in the modern world and thus the need to identify an effective treatment. The conventional treatments used in the management of cancer include chemotherapy and physiotherapy. These forms of cancer treatments usually have enormous side effects on the subjects. In this respect, an alternative form of treatment would be effective in managing cancer patients. A substantial number of natural products have been observed to be effective in the management of cancer. These natural products include plants and other natural substances such as honey. This study focuses on the efficiency of natural products in the treatment of cancer. Also, the anticancer effects of Peganum harmala, Manuka honey, and Saudi honey will be analyzed. Bee honey and Peganum harmala have been traditionally used in the treatment of cancer. The extracts from Peganum harmala plant have also been shown to exhibit divers’ antitumor effects similar to the mode of action of a vast number of anticancer agents. These established hypotheses thus give the rationale for this study. In this experiment, extracts were obtained from Peganum harmala leaves and exposed to cervical, lung, and prostate cancer cells. Similarly, solutions of Manuka honey and Saudi honey were exposed to the cervical, lung, and prostate cancer cells. The experiment duration was 24 hours, which obtained results were recorded and analyzed. Peganum harmala extracts inhibit cancer cell growth at different and achievable concentrations. Manuka honey highly inhibits the growth of HeLa cancer cells while Saudi honey highly inhibits the growth of A549 cells. Peganum harmala can form an effective treatment for managing several types of cancers. Manuka Honey can be applied as an effective treatment for managing cervical cancer while Saudi honey can form an effective treatment for managing lung cancers.

Anticancer Activity of Rice Callus Suspension Cultures from Aromatic Varieties and Metabolites Regulated in Treated Cancer Cell Lines

Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects.

Peptide-based boronates: How to achieve tissue specificity in anticancer therapy

Dipeptidyl boronic acids are suitable candidates for the design of "pro-soft" drugs because recent studies have proven that these acids undergo a p H-dependent cyclization equilibrium, generating an inactive cyclic form under physiological conditions. Dipeptidyl boronic acids possess a wide range of potential targets, and the 26 S proteasome appears to be one of the main targets.This multicatalytic complex is involved in intracellular protein turnover and is overexpressed in certain pathological conditions, such as malignancies, autoimmune diseases and neurodegenerative diseases. Bortezomib is the first-in-class derivative approved by the Food and Drug Administration for the treatment of hematological malignancies(i.e., relapsed and refractory multiple myeloma and mantle cell lymphoma) but is inactive against solid tumors due to an insufficient tissue distribution. The present study suggests a possible strategy for enhancing the in vivo performance of dipeptidyl boronic acids endowed with promising proteasomeinhibiting properties and their applicability as anticancer agents. In particular, dipeptidyl boronic acids might have a fruitful application as pro-soft drugs when an appropriate recognition motif serves as a substrate for a tumor-specific protease, generating the active form of the drug in situ and preventing systemic side effects after diffusion through cells and tissues.

Phytochemically Functionalized Cu and Ag Nanoparticles Embedded in MWCNTs for Enhanced Antimicrobial and Anticancer Properties

Nanomedicine is an emerging field concerned with the use of precision engineered nanomaterials, which leads to the development of novel remedial and diagnostic modalities for human use. In this study, Cu(NO_3)_2 and Ag NO_3 precursors were reduced to copper nanoparticles(Cu NPs) and silver nanoparticles(Ag NPs) using Terminalia arjuna bark extracts under microwave irradiation in the presence of well-dispersed multi-walled carbon nanotubes(MWCNTs) in aqueous medium. The formation of Cu NPs or Ag NPs and their functionalization with MWCNTs via bioactive molecules of plant extract were evidenced from UV–Vis spectra, XRD, FTIR, FESEM, EDX, and TEM images. The phytochemically functionalized Cu-MWCNTs and Ag-MWCNTs nanomaterials showed enhanced biocide activity, and the inhibitory activity for bacteria was higher than that of fungus. Furthermore, these biohybrid nanomaterials are non-toxic to normal epithelial cells(Vero), whereas they are highly toxic for tested human cancer cells of MDA-MB-231, He La, Si Ha, and Hep-G2. The cell viability was found to decrease with the increasing dose from 10 to 50 lg m L^(-1), as well as incubation time from 24 to 72 h. For instance, the cell viability was found to be *91 % for normal Vero cells and *76 % for cancer cells for lower dose of 10 lg m L^(-1).

Anticancer Effect of Ginseng Leaves Crude Polysaccharides on Human Hepatoma Cell SMMC-7721

Background: Polysaccharides extracted from the medicinal herbs are known to possess antitumor effects. Although there is a significant number of evidences implicated on the beneficial effects of the ginseng leaves ginsenoside with diverse associated mechanisms, reports on the anticancer by the ginseng leaves crude polysaccharides (GLCP) are not sufficient. Experiments were carried out to unravel the anticancer effects of GLCP. Methods: Cells were treated with GLCP (0.5 - 2 mg/ml) for 48h. MTT method was used to detect the cell viability. Western blot and flow cytometry were used to detect apoptotic rate. Western blot and acridine orange staining were used to detect the cell autophagy. Results: Compared with the normal human liver cell (Chang liver), GLCP (1.5 - 2 mg/ml) significantly reduction cell viability, promote apoptosis-related proteins expression, promote cell apoptosis and autophagy in SMMC-7721 cells. But caveolin-1 gene silencing could inhibit the anticancer effect of GLCP. Conclusions: These data suggest that GLCP promote autophagy and apoptosis in human hepatoma cell SMMC-7721. We speculate that its mechanism may be associated with the caveolin-1 which is an essential structural molecule of caveolae. Although the effect of GLCP inhibited of liver cancer is not very strong, we are more interested in the GLCP which plays a tumor suppressor role in health care.

Phytochemical profiling and anticancer potential of Cymbopogon citratus extract

Objective:To evaluate the anticancer potential of Cymbopogon citratus extract.Methods:GC-MS analysis was used to identify phytocomponents in the methanolic extract of Cymbopogon citratus.A fractionation method was employed to isolate and assess the bioactivity of different fractions and their cytotoxic activities against cancer cell lines HCT116,LoVo,Caco-2,and HT-29 were investigated.A dual staining method with acridine orange and ethidium bromide was used to assess the effect of the extract on cell apoptosis.Additionally,the expression levels of Bax and TP53 were quantified using real-time PCR in Caco-2 cells treated with the ethyl acetate fraction of Cymbopogon citratus extract.A protein array was employed to profile key pro-and anti-apoptotic proteins in Caco-2 cells.Moreover,molecular docking studies were conducted to investigate the interactions between key compounds of Cymbopogon citratus extract and specific apoptosis-related protein domains(PDB IDs:7wql and 4bkx).Results:A significant growth inhibition was observed in Caco-2 cells treated with Cymbopogon citratus extract.Among the seven fractions of the plant extract,the ethyl acetate fraction showed the highest cytotoxicity against Caco-2 cells with an IC50 value of(6.16±0.01)μg/mL.The immunofluorescence assay showed that the ethyl acetate fraction could induce apoptosis of Caco-2 cells.Moreover,the fraction upregulated the gene expressions of Bax and TP53 in a dose-dependent manner.The docking analysis demonstrated the interaction of five compounds isolated from the ethyl acetate fraction with key proteins in Caco-2 cells,indicating their anticancer properties.Conclusions:Cymbopogon citratus extract shows anticancer activity against Caco-2 cells by inducing apoptosis.It may be a promising candidate for the treatment of colon cancer,which needs further investigation.

Anticancer,Anti-inflammatory,Analgesic,and Anxiolytic Effects of Koumine and Their Molecular Mechanisms

Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and molecular mechanisms of koumine,with a particular emphasis on its mechanisms of action in the context of anticancer,anti-inflammatory,analgesic,and anxiolytic properties.The aim is to provide a theoretical foundation for further research and the application of koumine in clinical practice.

Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model

BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mainly treated with capecitabine chemotherapy regimen,supplemented by radiotherapy,immunotherapy and targeted therapy,but there are still limitations,so Chinese medicine plays an important role.AIM To investigate the effects of invigorating-spleen and anticancer prescription(ISAP)on body weight,tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway in CC mice model.METHODS The CC mice model were established and the mice were randomly divided into 5 groups,including the control group,capecitabine group,the low-dose,mediumdose and high-dose groups of ISAP,with 8 mice in each group,respectively.After 2 weeks of intervention,the body weight and tumor inhibition rate of mice were observed,and the expression of RAS,ERK,phosphorylated ERK(p-ERK),C-MYC and matrix metalloproteinase 2(MMP2)proteins in the tissues of tumors were detected.RESULTS Compared with the control group,the differences of body weight before and after treatment was much smaller in the groups of ISAP,with the smallest difference in the high-dose group of ISAP,while the capecitabine group had the greatest difference,indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice.The expression of RAS protein was decreased in the low-and medium-dose groups of ISAP,and the change of p-ERK was significant in the medium-and high-dose groups of ISAP.MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP.There were no significant changes in ERK in the ISAP group compared to the capecitabine group,while RAS,MMP2,and C-MYC protein expression were reduced in the ISAP group.The expression level of C-MYC protein decreased after treated with ISAP,and the decrease was the most significant in the medium-dose group of ISAP.CONCLUSION ISAP has a potential inhibiting effect on transplanted tumor in mice,and could maintain the general conditions,physical strength and body weight of mice.The expression levels of RAS,p-ERK,MMP2 and c-myc were also decreased to a certain extent.By inhibiting the expression of upstream proteins,the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased.Therefore,it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.

Factors Influencing Compliance with Safe Handling Requirements of Anticancer Agents by Nurses in a Tertiary Hospital-A Secondary Publication

Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.

Analysis of a Questionnaire Survey regarding Current Conditions against Exposure to Anticancer Drugs and Reports of Cancer Chemotherapy at Outpatient Departments in Japan

[Background] Medical staff have many occasions to be exposed to anticancer drugs (ACDs) in the process of performing cancer chemotherapy. Although guidelines for the safe handling of ACDs have been published, actual measures against exposure to ACDs differ between hospitals, and no surveillance data regarding the conditions of each hospital in relation to performing chemotherapy in Japan are available. [Methods] To understand current measures against exposure to ACDs and problems related to cancer chemotherapy at outpatient departments, we conducted a questionnaire survey on doctors, pharmacists, and nurses in 10 leading hospitals for cancer chemotherapy in Japan. [Results] Responses were received from all 10 institutions. The hospital pharmacists prepared all ACDs for outpatients in each institution. All hospitals took basic measures against ACD exposure, such as using personal protective equipment and penetration-resistant waste containers. Conditions against exposure to ACDs generally improved between 2012 and 2015, especially in terms of conveyance of ACDs and use of a closed-system drug transfer device. However, no measures linking ACDs with administration routes or injection sites were commonly taken in any of the hospitals in 2015. [Conclusions] Conditions against ACD exposure improved between 2012 and 2015, possibly because new guidelines were issued. To improve measures for ACD exposure in Japan, preparing more appropriate manuals and offering more opportunities to medical staff for continuing education are considered important.

Anticancer effect of the extracts from Polyalthia evecta against human hepatoma cell line(HepG2)

Objective:To investigate the anticancer activity of Polyalthia evecta(P.evecta)(Pierre) Finet & Gagnep against human hepatoma cell line(HepG2).Methods:The anticancer activity was based on(a) the cytotoxicity against human hepatoma cells(HepG2) assessed using a neutral red assay and(b) apoptosis induction determined by evaluation of nuclei morphological changes after DAP1 staining.Preliminary phytochemical analysis of the crude extract was assessed by HPLC analysis.Results:The 50% ethanol-water crude leaf extract of P.evecta(EW-L) showed greater potential anticancer activity with high cytotoxicity[IC_(50)=(62.8±7.3)μg/mL]and higher selectivity in HepG2 cells than normal Vero cells[selective index(SI)=7.9].The SI of EW-L was higher than the positive control,melphalan(SI=1.6) and the apoptotic cells(46.4±2.6)%induced by EW-L was higher than the melphalan(41.6±2.1)%(P<0.05).The HPLC chromatogram of the EW-L revealed the presence of various kinds of polyphenolics and flavonoids in it.Conclusions: P.evecta is a potential plant with anticancer activity.The isolation of pure compounds and determination of the bioactivity of individual compounds will be further performed.

Comparative investigation of the free radical scavenging potential and anticancer property of Diospyros blancoi(Ebenaceae)

Objective: To investigate the comparative effects of Diospyros blancoi(Ebenaceae)leaves(DBL), root bark(DBRB) and stem bark(DBSB) on free radicals and cancer.Methods: The polyphenol contents, antioxidant and free radical scavenging properties were determined using standard spectrophotometric methods. Cytotoxicity and anticancer activities were performed on brine shrimp nauplii and Ehrlich ascite carcinoma cells, respectively.Results: Among the extracts, DBSB showed the highest total antioxidant capacity and reducing capacity on ferrous ion. Based on 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radical scavenging activities, DBSB showed(95.760 ± 0.343)% and(67.460 ± 2.641)%scavenging with IC50of(3.10 ± 0.17) and(50.00 ± 3.11) mg/m L, respectively. The IC50 values of standard butylated hydroxytoluene and catechin(CA) for 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals were(8.50 ± 0.25) and(75.00 ± 0.14) mg/m L,respectively suggesting that DBSB had a significant(P < 0.05) radical scavenging activity than standards. In lipid peroxidation inhibition assay, the inhibitory activity of the extracts and the standard was in the following order: DBSB > DBRB > CA > DBL.Also, the phenolic [(139.91 ± 3.924) mg gallic acid equivalent/g] and flavonoid contents[(412.00 ± 16.70) mg catechin equivalent/g)] of DBSB were higher than that of other extracts. In addition, the DBSB showed the moderate cytotoxic and anticancer properties.Conclusions: Our results indicate that Diospyros blancoi stem bark had the significant highest antioxidant and free radical scavenging properties as well as moderate anticancer activity.Hence, we assume that the anticancer activity of this plant can be, at least in part, attributed to its content in phenolic compounds as well as its significant free radical scavenging properties.