Sesquiterpene lactone 6-O-angeloylplenolin reverses vincristine resistance by inhibiting YB-1 nuclear translocation in colon carcinoma cells.

Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy efficacy. In the present study, 6-O-angeloylplenolin repressed the overexpression of ATP binding cassette subfamily B member 1 () and increasing the intracellular concentration of anticancer drugs. A reduction in P-glycoprotein expression (encoded by ) was observed in parallel with a decline in mRNA expression in vincristine-resistant HCT (HCT-8/VCR) cells treated with 6-O-angeloylplenolin. In addition, 6-O-angeloylplenolin suppressed the activity of the gene promoter. Treatment with 6-O-angeloylplenolin also decreased the amount of the specific protein complex that interacted with the gene promoter in HCT-8/VCR cells, potentially leading to the suppression of expression. Treatment with 6-O-angeloylplenolin inhibited the nuclear translocation of Y-box binding protein-1 in HCT-8/VCR cells treated with 6-O-angeloylplenolin, contributing to the negative regulation of . Finally, 6-O-angeloylplenolin reversed VCR resistance in an HCT/VCR xenograft model. In conclusion, 6-O-angeloylplenolin exhibited a MDR-reversing effect by downregulating expression and could represent a novel adjuvant agent for chemotherapy.