To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-（2,3-dibromo-4,5-dihydroxybenzyl）-2,3-dibromo-4,5-dihydroxy benzyl methyl eth...To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-（2,3-dibromo-4,5-dihydroxybenzyl）-2,3-dibromo-4,5-dihydroxy benzyl methyl ether （1）, （＋）-3-（2,3-dibromo-4,5-dihydroxyphenyl）-4-bromo-5,6-dihydroxy-1,3- dihydroisobenzofuran （2）, 3-bromo-4-（2,3-dibromo-4,5-dihydroxybenzyl）-5-methoxymethyl-pyrocatechol （3）, 2,2＇,3,3＇-tetrabromo-4,4＇,5,5＇-tetrahydroxy-diphenylmethane （4）, bis（2,3-dibromo-4,5-dihydroxybenzyl） ether （5）, 2,2＇,3-tribromo-3＇,4,4＇,5-tetrahydroxy-6＇-ethyloxymethyldiphenylmethane （6） were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTF assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Be17402 and HCT-8. Their inhibitory activity against protein tyrosine kinase （PTK） with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana （EELN） was evaluated on S180-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC50 below 10 pg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4% respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer.展开更多
In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cu- cumber Holothuria atra is commonly known as the lollyfish. The antifimgal activity was detected using a...In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cu- cumber Holothuria atra is commonly known as the lollyfish. The antifimgal activity was detected using agar well diffusion method against the various fungal strains such as Trichoderma viride, Aspergillus niger, Aspergillus flavis, Candida albicans and Penicillium chrysogenum. Relatively high antifungal activity was seen against Candida albicans at 100 μL-1 concentration of extracts. Zone of inhibition was measured at 18 mm of diameter. The anti-tumor activities were detected against the Vero and Hep2 cell lines using MTT assay. The cells were treated with H. atra extract at concentrations 0.078-10mg mL-1. The extract showed high proliferative activity against the Hep2 cells. The body wall extracts of sea cucumber （H. atra） showed effective antifungal and antitumor activities All these findings suggest that the extracts could be used for the development of drugs.展开更多
AIM：To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS： Colorectal carcinoma （HT29） and human hepatocellular carcin...AIM：To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS： Colorectal carcinoma （HT29） and human hepatocellular carcinoma （HepG2） cells were treated with spray-dried extracts of Phyllanthus niruri （SDEPN） either alone or in combination with cisplatin at differ- ent concentrations （0.5 mg/mL and 1 mg/mL） for 4 h and 24 h. To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability, we stained the cells with prop- idium iodide and assessed them by flow cytometry. The percentage of cells in different cell cycle phases was quantified and data were expressed as histo- grams. Significant differences between groups were determined using analysis of variance and Bonferroni＇s test, as indicated. A value of P 〈 0.05 was considered to be statistically significant. RESULTS： SDEPN had significantly different cyto- toxic effects on HT29 （2.81 4- 0.11 vs 3.51 4- 1.13, P 〉 0.05） and HepG2 （5.07± 0.3 vs 15.9 ± 1.04, P 〈 0.001） cells when compared to control cells for 4 h. SDEPN also had significantly different cytotoxic effects on HT29 （1.91 ± 0.57 vs 4.53± 1.22, P 〉 0.05） and HepG2 （14.56 ± 1.6 vs 35.67 ± 3.94, P 〈 0.001） cells when compared to control cells for 24 h. Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells （HepG2 cells for 4 h： 10.78 ± 1.58 vs 53.89 ± 1.53, P 〈 0.001; 24 h： 8.9 ± 1.43 vs 62.78 ± 1.87, P 〈 0.001 and HT29 cells for 4 h： 9.52 ±0.913 vs 49.86 ± 2.89, P 〈 0.001; 24 h： 11.78 ± 1.05 vs 53.34 ± 2.65, P 〈 0.001）. In HT29 cells, pretreat- ment with SDEPN and subsequent treatment with cis-platin resulted in a greater number of cells being killed （12.78 ± 1.01 vs 93.76 ± 1.6, P 〈 0.001）. HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin （12.87 ± 2.78 vs 78.8 ± 3.02, P 〈 0.001）. CONCLUSION： SDEPN is selectively toxic against two cancer cell lines. Moreover, SDEPN in combination with cisplatin induces a synergistic increase in the cell death of both HT29 and HepG2 cells.展开更多
AIM:To study the inhibition of tumor angiogenesis by 5,2,4'-trihydroxy-6,7,5'-trimethoxyflavone(TTF1) isolated from an extract of herbal medicine Sorbaria sorbifolia.METHODS:Angiogenic activity was assayed usi...AIM:To study the inhibition of tumor angiogenesis by 5,2,4'-trihydroxy-6,7,5'-trimethoxyflavone(TTF1) isolated from an extract of herbal medicine Sorbaria sorbifolia.METHODS:Angiogenic activity was assayed using the chick embryo chorioallantoic membrane(CAM) method.Microvessel density(MVD) was determined by staining tissue sections immunohistochemically for CD34 using the Weidner capillary counting method.The mRNA and protein levels of vascular endothelial growth factor(VEGF),vascular endothelialgrowth factor receptor 2(VEGFR2,Flk-1/KDR),basic fibroblast growth factor(bFGF),cyclo-oxygenase(COX)-2 and hypoxia-inducible factor(HIF)-1α were detected by quantitative real-time polymerase chain reaction and Western blotting analysis.RESULTS:The TTF1 inhibition rates for CAM were 30.8%,38.2% and 47.5% with treatment concentrations of 25,50 and 100 μg/embryo × 5 d,respectively.The inhibitory rates for tumor size were 43.8%,49.4% and 59.6% at TTF1 treatment concentrations of 5,10,and 20 μmol/kg,respectively.The average MVD was 14.2,11.2 and 8.5 at treatment concentrations of 5 μmol/kg,10 μmol/kg and 20 μmol/kg TTF1,respectively.The mRNA and protein levels of VEGF,KDR,bFGF,COX-2 and HIF-1α in mice treated with TTF1 were significantly decreased.CONCLUSION:TTF1 can inhibit tumor angiogenesis,and the mechanism may be associated with the down-regulation of VEGF,KDR,bFGF,HIF-1α and COX-2.展开更多
To evaluate the antitumor activity of Lactuca serriola against EAC （Ehrlich ascites carcinoma） in Swiss albino mice. The in vivo antitumor activity of the methanol extract of plant Lactuca serriola was evaluated at ...To evaluate the antitumor activity of Lactuca serriola against EAC （Ehrlich ascites carcinoma） in Swiss albino mice. The in vivo antitumor activity of the methanol extract of plant Lactuca serriola was evaluated at （100 mg/kg and 200 mg/kg of hole plant and 200 mg/kg, 400 mg/kg of fruit bw） against EAC using mean survival time. After administration of the extracts of Lactuca serriola, viable EAC cell count and body weight in the EAC tumor hosts were observed. The animal was also observed for improvement in the hematological parameters （e.g., hemoglobin content, red and white blood cells count and differential cell count） after treatment of plant extract. Intraperitoneal administration of plant extracts reduced viable EAC cells, increased the survival time and restored altered hematological parameters. Significant efficacy was observed for fruit extract at high concentration 400 mg/kg dose （P 〈 0.05）. It can be concluded that the methyl extract ofLactuca serriola possesses significant antitumor activity.展开更多
OBJECTIVE： To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription -- Qingyihuaji formula （QYHJ） -- from Traditional Chinese Medicine （TCM...OBJECTIVE： To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription -- Qingyihuaji formula （QYHJ） -- from Traditional Chinese Medicine （TCM）.METHODS： Nude mice were implanted subcutaneously with human pancreatic cancer cell line SW1990 and then randomly divided into four groups： Control, QYHJ extract, Gemcitabine, and Combination of QYHJ extract and gemcitabine. Treatments were given for 21 days and tumor growth was evaluated simultaneously. Then, expression of Notch receptors （Notch-I, Notch-2, Notch-3, and Notch-4） and their Jagged ligands （Jagged-1 and Jagged-2） in dissected tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Finally, immunohistochemistry was performed to detect CD133, a marker of pancreatic cancer stem cells （CSCs）, to evaluate the impact of QYHJ extract on pancreatic CSCs.RESULTS： QYHJ extract treatment effectively inhib- ited the tumor growth in nude mice. The expression of both Notch-4 and Jagged-1 were decreased significantly in QYHJ treatment groups （P 〈 0.05）, while gemcitabine alone had no significant effect in down-regulating Jagged-1 （P 〉 0.05）. No significant difference was observed in the ex- pression of Notch-1, Notch-2, Notch-3, and Jagged-2 between three treatment groups and control group （P 〉 0.05）. Moreover, immunohistochemical analysis showed that the number of CD133 positive cells was significantly reduced by QYHJ treatment （P 〈 0.05）, and the combined treatment was more effective than gemcitabine alone （P 〈 0.05）.CONCLUSION： The role of the extract in pancreatic cancer treatment was associated with down-regulation of Notch-4 and Jagged-1 in Notch signaling pathway. The extract could enhance the antitumor activity of gemcitabine and was more effective than gemcitabine in regulating Notch signaling pathway to some extent.展开更多
tract in external use on expression of proto-onco- genes her2 and tumor suppression genes p16 in rat breast tissues of mammary hyperplasia model. To explore the mechanisms of Rupifang Extract in external use for preve...tract in external use on expression of proto-onco- genes her2 and tumor suppression genes p16 in rat breast tissues of mammary hyperplasia model. To explore the mechanisms of Rupifang Extract in external use for preventing and treating mammary hyperplasia. METHODS Thirty virginal female Wistar rats were randomized into 5 groups, 6 in each, A： blank con- trol group; B： model group; C： the low dose group of Rupifang; D： the middle dose group of Rupifang; and E： The high dose group of Rupifang. The mam- mary hyperplasia rat models were produced by in- jecting estradiol benzoate and progesterone and ir- ritating by tail nipping. Drug intervention was also launched during the model formation. After 30 days, the expression of her2 and p16 in breast tis- sues of rats in each group were detected by the SP immunohistochemical method. RESULTS： Compared with Blank control group, the expression of her2 in breast tissues in Model group was higher, and the expression of p16 was lower （P〈O.05 or P〈O.01）. After intervention with Rupi- fang Extract, compared with Model group, the ex- pression of her2 in breast tissues in Rupifang groups was lower, and the expression of p16 higher （P〈O.05 or P〈O.01）. CONCLUSION： The mechanisms of Rupifang Ex- tract in external application for preventing and treating mammary hyperplasia may be reducing the expression of proto-oncogenes her2 and in- creasing the expression of tumor suppression genes p16.展开更多
基金Supported by the National High Technology Research and Development Program of China (863 Program, No. 2007AA09Z410)Knowledge Innovation Program of Chinese Academy of Sciences (No. KZCX2-YW-209)
文摘To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-（2,3-dibromo-4,5-dihydroxybenzyl）-2,3-dibromo-4,5-dihydroxy benzyl methyl ether （1）, （＋）-3-（2,3-dibromo-4,5-dihydroxyphenyl）-4-bromo-5,6-dihydroxy-1,3- dihydroisobenzofuran （2）, 3-bromo-4-（2,3-dibromo-4,5-dihydroxybenzyl）-5-methoxymethyl-pyrocatechol （3）, 2,2＇,3,3＇-tetrabromo-4,4＇,5,5＇-tetrahydroxy-diphenylmethane （4）, bis（2,3-dibromo-4,5-dihydroxybenzyl） ether （5）, 2,2＇,3-tribromo-3＇,4,4＇,5-tetrahydroxy-6＇-ethyloxymethyldiphenylmethane （6） were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTF assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Be17402 and HCT-8. Their inhibitory activity against protein tyrosine kinase （PTK） with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana （EELN） was evaluated on S180-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC50 below 10 pg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4% respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer.
文摘In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cu- cumber Holothuria atra is commonly known as the lollyfish. The antifimgal activity was detected using agar well diffusion method against the various fungal strains such as Trichoderma viride, Aspergillus niger, Aspergillus flavis, Candida albicans and Penicillium chrysogenum. Relatively high antifungal activity was seen against Candida albicans at 100 μL-1 concentration of extracts. Zone of inhibition was measured at 18 mm of diameter. The anti-tumor activities were detected against the Vero and Hep2 cell lines using MTT assay. The cells were treated with H. atra extract at concentrations 0.078-10mg mL-1. The extract showed high proliferative activity against the Hep2 cells. The body wall extracts of sea cucumber （H. atra） showed effective antifungal and antitumor activities All these findings suggest that the extracts could be used for the development of drugs.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq (470179/2009-0) for financial support and Postgraduate Program in Pharmaceutical Sciences,Federal University of Rio Grande do Norte
文摘AIM：To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS： Colorectal carcinoma （HT29） and human hepatocellular carcinoma （HepG2） cells were treated with spray-dried extracts of Phyllanthus niruri （SDEPN） either alone or in combination with cisplatin at differ- ent concentrations （0.5 mg/mL and 1 mg/mL） for 4 h and 24 h. To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability, we stained the cells with prop- idium iodide and assessed them by flow cytometry. The percentage of cells in different cell cycle phases was quantified and data were expressed as histo- grams. Significant differences between groups were determined using analysis of variance and Bonferroni＇s test, as indicated. A value of P 〈 0.05 was considered to be statistically significant. RESULTS： SDEPN had significantly different cyto- toxic effects on HT29 （2.81 4- 0.11 vs 3.51 4- 1.13, P 〉 0.05） and HepG2 （5.07± 0.3 vs 15.9 ± 1.04, P 〈 0.001） cells when compared to control cells for 4 h. SDEPN also had significantly different cytotoxic effects on HT29 （1.91 ± 0.57 vs 4.53± 1.22, P 〉 0.05） and HepG2 （14.56 ± 1.6 vs 35.67 ± 3.94, P 〈 0.001） cells when compared to control cells for 24 h. Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells （HepG2 cells for 4 h： 10.78 ± 1.58 vs 53.89 ± 1.53, P 〈 0.001; 24 h： 8.9 ± 1.43 vs 62.78 ± 1.87, P 〈 0.001 and HT29 cells for 4 h： 9.52 ±0.913 vs 49.86 ± 2.89, P 〈 0.001; 24 h： 11.78 ± 1.05 vs 53.34 ± 2.65, P 〈 0.001）. In HT29 cells, pretreat- ment with SDEPN and subsequent treatment with cis-platin resulted in a greater number of cells being killed （12.78 ± 1.01 vs 93.76 ± 1.6, P 〈 0.001）. HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin （12.87 ± 2.78 vs 78.8 ± 3.02, P 〈 0.001）. CONCLUSION： SDEPN is selectively toxic against two cancer cell lines. Moreover, SDEPN in combination with cisplatin induces a synergistic increase in the cell death of both HT29 and HepG2 cells.
基金Supported by The National Natural Science Foundation Grant,No. 30860374
文摘AIM:To study the inhibition of tumor angiogenesis by 5,2,4'-trihydroxy-6,7,5'-trimethoxyflavone(TTF1) isolated from an extract of herbal medicine Sorbaria sorbifolia.METHODS:Angiogenic activity was assayed using the chick embryo chorioallantoic membrane(CAM) method.Microvessel density(MVD) was determined by staining tissue sections immunohistochemically for CD34 using the Weidner capillary counting method.The mRNA and protein levels of vascular endothelial growth factor(VEGF),vascular endothelialgrowth factor receptor 2(VEGFR2,Flk-1/KDR),basic fibroblast growth factor(bFGF),cyclo-oxygenase(COX)-2 and hypoxia-inducible factor(HIF)-1α were detected by quantitative real-time polymerase chain reaction and Western blotting analysis.RESULTS:The TTF1 inhibition rates for CAM were 30.8%,38.2% and 47.5% with treatment concentrations of 25,50 and 100 μg/embryo × 5 d,respectively.The inhibitory rates for tumor size were 43.8%,49.4% and 59.6% at TTF1 treatment concentrations of 5,10,and 20 μmol/kg,respectively.The average MVD was 14.2,11.2 and 8.5 at treatment concentrations of 5 μmol/kg,10 μmol/kg and 20 μmol/kg TTF1,respectively.The mRNA and protein levels of VEGF,KDR,bFGF,COX-2 and HIF-1α in mice treated with TTF1 were significantly decreased.CONCLUSION:TTF1 can inhibit tumor angiogenesis,and the mechanism may be associated with the down-regulation of VEGF,KDR,bFGF,HIF-1α and COX-2.
文摘To evaluate the antitumor activity of Lactuca serriola against EAC （Ehrlich ascites carcinoma） in Swiss albino mice. The in vivo antitumor activity of the methanol extract of plant Lactuca serriola was evaluated at （100 mg/kg and 200 mg/kg of hole plant and 200 mg/kg, 400 mg/kg of fruit bw） against EAC using mean survival time. After administration of the extracts of Lactuca serriola, viable EAC cell count and body weight in the EAC tumor hosts were observed. The animal was also observed for improvement in the hematological parameters （e.g., hemoglobin content, red and white blood cells count and differential cell count） after treatment of plant extract. Intraperitoneal administration of plant extracts reduced viable EAC cells, increased the survival time and restored altered hematological parameters. Significant efficacy was observed for fruit extract at high concentration 400 mg/kg dose （P 〈 0.05）. It can be concluded that the methyl extract ofLactuca serriola possesses significant antitumor activity.
基金Supported by the National Natural Science Foundation of China(No.81173461)China Scholarship Council(No.201306100055)
文摘OBJECTIVE： To investigate, in terms of Notch signaling pathway, the effect on pancreatic cancer of the extract of an anti-tumor prescription -- Qingyihuaji formula （QYHJ） -- from Traditional Chinese Medicine （TCM）.METHODS： Nude mice were implanted subcutaneously with human pancreatic cancer cell line SW1990 and then randomly divided into four groups： Control, QYHJ extract, Gemcitabine, and Combination of QYHJ extract and gemcitabine. Treatments were given for 21 days and tumor growth was evaluated simultaneously. Then, expression of Notch receptors （Notch-I, Notch-2, Notch-3, and Notch-4） and their Jagged ligands （Jagged-1 and Jagged-2） in dissected tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Finally, immunohistochemistry was performed to detect CD133, a marker of pancreatic cancer stem cells （CSCs）, to evaluate the impact of QYHJ extract on pancreatic CSCs.RESULTS： QYHJ extract treatment effectively inhib- ited the tumor growth in nude mice. The expression of both Notch-4 and Jagged-1 were decreased significantly in QYHJ treatment groups （P 〈 0.05）, while gemcitabine alone had no significant effect in down-regulating Jagged-1 （P 〉 0.05）. No significant difference was observed in the ex- pression of Notch-1, Notch-2, Notch-3, and Jagged-2 between three treatment groups and control group （P 〉 0.05）. Moreover, immunohistochemical analysis showed that the number of CD133 positive cells was significantly reduced by QYHJ treatment （P 〈 0.05）, and the combined treatment was more effective than gemcitabine alone （P 〈 0.05）.CONCLUSION： The role of the extract in pancreatic cancer treatment was associated with down-regulation of Notch-4 and Jagged-1 in Notch signaling pathway. The extract could enhance the antitumor activity of gemcitabine and was more effective than gemcitabine in regulating Notch signaling pathway to some extent.
基金Supported by China National Foundation of Natural Science(Project No.81173265)Foundation of Natural Science of Guangdong Province(Project No.10151063201000065)+11 种基金Science and Technology Plan Projects of Guangdong Province(No:2009B0308012382012B031800155)The Fundamental Research Funds for the Central Universities (No.21612422216113119)Guangzhou Municipal Planned Science and Technology Project(No.2009Z1-E091)Guangdong Provincial Administration of Traditional Chinese Medicine(No.201111752008092)Guangdong University Students' Innovation Experimental Program(No.1055910014)Jinan University's the National Collegiate Innovation Experimental Program,2010(No.101055916)Jinan University's Cultivation Project of Scientific Research Creation for Outstanding Undergraduates Recommended for Post-graduate StudyJinan University's the National Collegiate Innovation and Startups Training Program(No.1210559029)Jinan University's 211 Engineering Construction Program
文摘tract in external use on expression of proto-onco- genes her2 and tumor suppression genes p16 in rat breast tissues of mammary hyperplasia model. To explore the mechanisms of Rupifang Extract in external use for preventing and treating mammary hyperplasia. METHODS Thirty virginal female Wistar rats were randomized into 5 groups, 6 in each, A： blank con- trol group; B： model group; C： the low dose group of Rupifang; D： the middle dose group of Rupifang; and E： The high dose group of Rupifang. The mam- mary hyperplasia rat models were produced by in- jecting estradiol benzoate and progesterone and ir- ritating by tail nipping. Drug intervention was also launched during the model formation. After 30 days, the expression of her2 and p16 in breast tis- sues of rats in each group were detected by the SP immunohistochemical method. RESULTS： Compared with Blank control group, the expression of her2 in breast tissues in Model group was higher, and the expression of p16 was lower （P〈O.05 or P〈O.01）. After intervention with Rupi- fang Extract, compared with Model group, the ex- pression of her2 in breast tissues in Rupifang groups was lower, and the expression of p16 higher （P〈O.05 or P〈O.01）. CONCLUSION： The mechanisms of Rupifang Ex- tract in external application for preventing and treating mammary hyperplasia may be reducing the expression of proto-oncogenes her2 and in- creasing the expression of tumor suppression genes p16.
