Huang, SuBijangi-Vishehsaraei, KhadijehSaadatzadeh, Mohammad RezaSafa, Ahmad R.2016-06-282016-06-282012-10Huang, S., Bijangi-Vishehsaraei, K., Saadatzadeh, M. R., & Safa, A. R. (2012). Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells. Journal of Cancer Therapy, 3(5), 504–510. http://doi.org/10.4236/jct.2012.35065https://hdl.handle.net/1805/10228BACKGROUND: Taxol (paclitaxel) inhibits proliferation and induces apoptosis in a variety of cancer cells, but it also upregulates cytoprotective proteins and/or pathways that compromise its therapeutic efficacy. MATERIALS AND METHOD: The roles of GM3 synthase (α2,3-sialyltransferase, ST3Gal V) in attenuating Taxol-induced apoptosis and triggering drug resistance were determined by cloning and overexpressing this enzyme in the SKOV3 human ovarian cancer cell line, treating SKOV3 and the transfectants (SKOV3/GS) with Taxol and determining apoptosis, cell survival, clonogenic ability, and caspase-3 activation. RESULTS: In this report, we demonstrated that Taxol treatment resulted in apoptosis which was associated with caspase-3 activation. Taxol treatment upregulated the expression of human GM3 synthase, an enzyme that transfers a sialic acid to lactosylceramide. Moreover, we cloned the full-length GM3 synthase gene and showed for the first time that forced expression of GM3 synthase attenuated Taxol-induced apoptosis and increased resistance to Taxol in SKOV3 cells. CONCLUSIONS: GM3 synthase overexpression inhibited Taxol-triggered caspase-3 activation, revealing that upregulation of GM3 synthase prevents apoptosis and hence reduces the efficacy of Taxol therapy.en-USPublisher PolicyApoptosisCaspase-8Drug resistanceGM3 synthaseOvarian cancerTaxolArticle