INCREASING SENSITIVITY OF MCF-7/DOX CELLS TOWARDSDOXORUBICIN BY HESPERETIN THROUGH SUPPRESSION OFP-GLYCOPROTEIN EXPRESSION
Penulis/Author
SARMOKO (1); DYANINGTYAS DEWI PAMUNGKAS PUTRI (2); Prof. Dr. apt. Ratna Asmah Susidarti, MS. (3); Prof. Dr. apt. Agung Endro Nugroho, S.Si., M.Si. (4); Prof. Dr. apt. Edy Meiyanto, M.Si. (5)
Tanggal/Date
2014
Kata Kunci/Keyword
Abstrak/Abstract
Long-term use of doxorubicin causes cancer resistance due
to overexpression of P-glycoprotein (P-gp), a protein that plays a
role in cell drug efflux. The purpose of this study is to determine
the action of hesperetin in increasing the cytotoxicity of
doxorubicin on MCF-7 cancer cells resistant to doxorubicin (MCF-
7/DOX) through suppression of P-gp expression. Cytotoxic assay
of single and combinational treatment of doxorubicin and
hesperetin were performed by using MTT assay. Apoptosis
evidence was examined by using double staining with acridine
orange and ethidium bromide dyes, while Pgp expression was
determined by using immunocytochemistry. Hesperetin reduced
cell viability in dose dependent manner. Both MCF-7 ori and
MCF-7/DOX cells gave different responses to hesperetin with the
IC50 values of >500?M and 267?M, respectively. Combining
treatment of hesperetin and doxorubicin to MCF-7/DOX cells at
the dose of 95?M and 230nM increased apoptosis evidence and
suppressed P-gp expression. These results suggest that
hesperetin enhances the anticancer effect of doxorubicin to
resistance MCF-7 cells through suppression of P-gp expression
