Human beta-galactoside alpha-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity.
Taxol triggers apoptosis in a variety of cancer cells, but it also upregulates cytoprotective proteins and/or pathways that compromise its therapeutic efficacy. In this report, we found that Taxol treatment resulted in caspase-8-dependent apoptosis in SKOV3 human ovarian cancer cells. Moreover, Taxol-induced apoptosis was associated with caspase-3 activation. Interestingly, Taxol treatment upregulated alpha-2,3-sialyltransferase (ST3Gal III) expression and forced expression of ST3Gal III attenuated Taxol-induced apoptosis. Furthermore, ST3Gal III overexpression inhibited Taxol-triggered caspase-8 activation, indicating that ST3Gal III upregulation produces cellular resistance to Taxol and hence reduces the efficacy of Taxol therapy.
Huang
Su
S
Department of Pharmacology and Toxicology, Indiana University Simon Cancer Center, Indiana University School of Medicine, 1044 West Walnut St. R4-119, Indianapolis, IN 46202, USA.
Day
Travis W
TW
Choi
Mi-Ran
MR
Safa
Ahmad R
AR
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D012799:Sialyltransferases / Q000096:biosynthesis / Q000378:metabolism*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D012799:Sialyltransferases; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D017239:Paclitaxel; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human