Inhibition of protein glycosylation reverses the MDR phenotype of cancer cell lines
Abstract
Multidrug resistance proteins are one of the most important factors that cause chemotherapy resistance, which in turn reduces therapeutic efficacy and survival for cancer patients. Tunicamycin is one of the most well-known inhibitors of N-glycosylation and is considered a powerful adjunct that can increase the effectiveness of many drugs. Tunicamycin blocks the first step of P-gp (glycoprotein P) and BCRP (breast cancer resistance protein) N-glycosylation, which is a very important modification for the activity and cellular localisation of these proteins. The effects of tunicamycin on ovarian and colorectal cancer cells were examined in multiple cell lines. The primary ovarian cancer cell line W1 and the established ovarian cancer cell line A2780 were compared against their drug-resistant derivatives W1TR/W1PR (TR: topotecan resistant; PR: paclitaxel resistant) and A2780T1 (topotecan resistant), respectively. We also compared the colorectal cancer cell line LoVo against its doxorubicin-resistant derivative LoVo/Dx. Cell viability was determined by the MTT assay. The glycopeptides were subjected to deglycosylation using the endoglycosidase PNGase F. A2780T1, LoVo/Dx and W1PR cells were treated with the protein degradation inhibi...Continue Reading
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