Abstract
Multidrug resistance (MDR) is a prime reason for numerous failed oncotherapy approaches. In the present study, we investigated whether Alisol F 24 acetate (ALI) could reverse the MDR of MCF-7/DOX cells, a multidrug-resistant human breast cancer cell line. We found that ALI was a potent P-glycoprotein (P-gp) inhibitor, in the Caco-2-monolayer cell model. ALI showed a significant and concentration-dependent cytotoxic effect on MCF-7/DOX cells in combination with doxorubicin by increasing intracellular accumulation and inducing nuclear migration of doxorubicin. However, ALI had no such effect on MCF-7 cells. In addition, ALI also promoted doxorubicin-induced early apoptosis of MCF-7/DOX cells in a time-dependent manner. These results suggest that ALI can enhance chemosensitivity of doxorubicin and reinforce its anti-cancer effect by increasing its uptake, especially inducing its nuclear accumulation in MCF-7/DOX cells. Therefore, ALI could be developed as a potential MDR-reversing agent in cancer chemotherapy in further study.
Highlights
One challenge faced by cancer chemotherapy is the development of multidrug resistance (MDR) [1]
We investigated the pharmacological function of doxorubicin to further the pharmacological function of doxorubicin to further confirm above results
ALI reported that P-gp has several effects including toxic xenobiotics by excreting reversing
Summary
One challenge faced by cancer chemotherapy is the development of multidrug resistance (MDR) [1]. After a long-term exposure to anticancer drugs in malignant tumor cells, MDR cells acquire resistance to one chemotherapeutic drug, and and may become resistant to some other anticancer drugs featuring different structures and functions [2]. A wide range of structurally diverse drugs used to treat cancer are extruded from cells, including doxorubicin, vinblastine, epipodophyllotoxins and paclitaxel [3]. Efflux proteins that mediate MDR of cancer cells are mainly the superfamily of adenosine triphosphate binding cassette-(ABC) transporters, including P-glycoprotein (P-gp) [4], multi-drug resistance protein (MRP) [5] and breast cancer resistance protein (BCRP) [6,7]. P-gp increases efflux of anticancer drugs, reducing intracellular drug levels and causing consequent drug insensitivity [9,10]
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