title: In vitro modulation of P-glycoprotein, MRP-1 and BCRP expression by mangiferin in doxorubicin-treated MCF-7 cells.
abstract: The multidrug resistance phenotype is one of the major problems in development of cancer cell resistance to chemotherapy. Some natural compounds from medicinal plants have demonstrated promising capacity in enhancing anticancer effects in drug resistant cancer cells. We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), MRP1 and BCRP. We exposed MCF-7 breast cancer cells pretreated with doxorubicin for 10 days to mangiferin (10, 25 or 50 μM) for 96 hours. Afterwards, we evaluated influence on cell viability and level of mRNA expression of P-gp, MRP1 and BCRP. Doxorubicin given in combination with mangiferin at low concentrations (10 and 25 μM) failed to give significant reduction in cell viability, while at the highest concentrations, the combination significantly reduced cell viability. The mRNA expression analysis of P-gp, MRP1 and BCRP showed that mangiferin had inhibitory effects on P-gp but no effects on MRP1 and BCRP. In conclusion, we suggest that mangiferin at high concentrations can be used as chemosensitizer for doxorubicin therapy. This effect might be attributed by inhibitory effects of mangiferin on P-glycoprotein expression.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia E-mail : melva.louisa@gmail.com.
authors.forename: Melva
authors.initials: M
authors.lastname: Louisa
authors.forename: Tjahjani Mirawati
authors.initials: TM
authors.lastname: Soediro
authors.forename: Frans Dhyanagiri
authors.initials: FD
authors.lastname: Suyatna
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D031022:Mangifera / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D028321:Plant Preparations / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D028321:Plant Preparations; D012333:RNA, Messenger; D044004:Xanthones; C116614:ABCG2 protein, human; C013592:mangiferin; C421109:multidrug resistance-associated protein 1