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A multidrug resistance-associated protein inhibitor is a potential enhancer of the benzyl isothiocyanate-induced apoptosis induction in human colorectal cancer cells.
- Source :
-
Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2021 Jul; Vol. 35 (7), pp. e22791. Date of Electronic Publication: 2021 Apr 21. - Publication Year :
- 2021
-
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.<br /> (© 2021 Wiley Periodicals LLC.)
- Subjects :
- HCT116 Cells
Humans
Multidrug Resistance-Associated Proteins metabolism
Apoptosis drug effects
Colorectal Neoplasms drug therapy
Colorectal Neoplasms metabolism
Colorectal Neoplasms pathology
Isothiocyanates pharmacokinetics
Isothiocyanates pharmacology
Multidrug Resistance-Associated Proteins antagonists & inhibitors
Propionates pharmacology
Quinolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1099-0461
- Volume :
- 35
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of biochemical and molecular toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 33880814
- Full Text :
- https://doi.org/10.1002/jbt.22791