A multidrug resistance-associated protein inhibitor is a potential enhancer of the benzyl isothiocyanate-induced apoptosis induction in human colorectal cancer cells.
Qifu YangToshiyuki NakamuraMasayuki SetoMiku MiyagawaWensi XuBeiwei ZhuShintaro MunemasaYoshiyuki MurataYoshimasa NakamuraPublished in: Journal of biochemical and molecular toxicology (2021)
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.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- endothelial cells
- oxidative stress
- high glucose
- cell cycle arrest
- signaling pathway
- diabetic rats
- induced pluripotent stem cells
- cell death
- drug induced
- pluripotent stem cells
- emergency department
- squamous cell carcinoma
- cell proliferation
- climate change
- replacement therapy