A multidrug resistance‐associated protein inhibitor is a potential enhancer of the benzyl isothiocyanate‐induced apoptosis induction in human colorectal cancer cells

Abstract

The increasing drug efflux through the ATP-binding cassette (ABC) transporters is the most plausible mechanism that mediates resistance to the anticancer phytochemicals, such as benzyl isothiocyanate (BITC), as well as chemotherapy drugs. To identify a potential component to overcome this resistance by combinatory utilization, we focused on multidrug resistance-associated proteins (MRPs) pumping various drug metabolites with glutathione as well as the organic anions. The pharmacological treatment of an MRP inhibitor, MK571, significantly potentiated the BITC-induced antiproliferation, coincided with the enhanced accumulation of BITC and glutathione in human colorectal cancer HCT-116 cells. MK571 also enhanced the apoptosis induction as well as activation of the mitogen-activated protein kinases and caspase-3, whereas it did not affect their basal levels. These results suggested that, since MRPs might play a pivotal role in the BITC efflux, MK571 potentiates the BITC-induced antiproliferation in human colorectal cancer cells through inhibition of the glutathione-dependent BITC efflux.

Gastrointestinal Tumors: Phytochemical and Drug Combinations Targeting the Hallmarks of Cancer

“…Synergy effect is broadly defined as the interaction or cooperation of two or more substances to produce a combined effect greater than the sum of their individual effects [34]. Combinational treatment with phytochemicals and anticancer drugs can suppress cancer recurrence and reduce the resistance of tumor cells to chemotherapeutic agents [35]. Interestingly, green beet and red beetroot have been described as vegetables rich in phytochemicals with anticancer effects, like vitexin-2-O-xyloside, apigenin, betacyanins, betaxanthins, which possess antitumor properties against colon, liver and bladder cancers [36].…”