Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells
dc.contributor.author | Huang, Su | |
dc.contributor.author | Bijangi-Vishehsaraei, Khadijeh | |
dc.contributor.author | Saadatzadeh, Mohammad Reza | |
dc.contributor.author | Safa, Ahmad R. | |
dc.contributor.department | Department of Pharmacology and Toxicology, IU School of Medicine | en_US |
dc.date.accessioned | 2016-06-28T19:14:34Z | |
dc.date.available | 2016-06-28T19:14:34Z | |
dc.date.issued | 2012-10 | |
dc.description.abstract | BACKGROUND: 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_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Huang, 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.2012.35065 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/10228 | |
dc.language.iso | en_US | en_US |
dc.publisher | Scientific Research | en_US |
dc.relation.isversionof | 10.4236/jct.2012.35065 | en_US |
dc.relation.journal | Journal of Cancer Therapy | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Apoptosis | en_US |
dc.subject | Caspase-8 | en_US |
dc.subject | Drug resistance | en_US |
dc.subject | GM3 synthase | en_US |
dc.subject | Ovarian cancer | en_US |
dc.subject | Taxol | en_US |
dc.title | Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells | en_US |
dc.type | Article | en_US |