@article{ebb562118ca84457bc61341df641526c,
title = "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.",
keywords = "MK571, apoptosis, benzyl isothiocyanate, colorectal cancer, multidrug resistance-associated proteins",
author = "Qifu Yang and Toshiyuki Nakamura and Masayuki Seto and Miku Miyagawa and Wensi Xu and Beiwei Zhu and Shintaro Munemasa and Yoshiyuki Murata and Yoshimasa Nakamura",
note = "Funding Information: This study was supported in part by MEXT KAKENHI Grant Numbers 17H03818 and 20H02933 (YN). Some part of this paper has been taken from the PhD thesis of the first author, Qifu Yang (Yang, Q. Synergistic antiproliferative effects of benzyl isothiocyanate in combination with methyl‐β‐cyclodextrin and MK571 in human colorectal cancer cells. PhD thesis, The Graduate School of Environmental and Life Science, Okayama University, Japan, 1‐54 (2018)), which has been open before the acceptance of this paper. Funding Information: This study was supported in part by MEXT KAKENHI Grant Numbers 17H03818 and 20H02933 (YN). Some part of this paper has been taken from the PhD thesis of the first author, Qifu Yang (Yang, Q. Synergistic antiproliferative effects of benzyl isothiocyanate in combination with methyl-?-cyclodextrin and MK571 in human colorectal cancer cells. PhD thesis, The Graduate School of Environmental and Life Science, Okayama University, Japan, 1-54 (2018)), which has been open before the acceptance of this paper. Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC",
year = "2021",
month = jul,
doi = "10.1002/jbt.22791",
language = "English",
volume = "35",
journal = "Journal of Biochemical and Molecular Toxicology",
issn = "1095-6670",
publisher = "John Wiley and Sons Inc.",
number = "7",
}
