A multidrug resistance-associated protein inhibitor is a potential enhancer of the benzyl isothiocyanate-induced apoptosis induction in human colorectal cancer cells
| Autor: | Wensi Xu, Yoshiyuki Murata, Beiwei Zhu, Masayuki Seto, Miku Miyagawa, Qifu Yang, Yoshimasa Nakamura, Shintaro Munemasa, Toshiyuki Nakamura |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis Apoptosis Toxicology Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Isothiocyanates Humans Molecular Biology 030102 biochemistry & molecular biology Kinase Benzyl isothiocyanate General Medicine Glutathione HCT116 Cells Multiple drug resistance chemistry 030220 oncology & carcinogenesis Cancer research Quinolines Molecular Medicine Efflux Multidrug Resistance-Associated Proteins Propionates Colorectal Neoplasms Drug metabolism |
| Zdroj: | Journal of biochemical and molecular toxicologyREFERENCES. 35(7) |
| ISSN: | 1099-0461 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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