Abstract
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. 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. 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. 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.
Highlights
Epithelial ovarian cancer is the major cause of death in women with gynecological malignancies [1]
We explored whether Taxol treatment increased the expression of GM3 synthase in SKOV3 human ovarian cancer cells, and whether forced expression affected the sensitivity of these cells to apoptosis, thereby altering the efficacy of Taxol therapy
We have found that Taxol at 100 - 500 nM induces robust apoptosis in cell lines from different types of cancer [22]
Summary
Epithelial ovarian cancer is the major cause of death in women with gynecological malignancies [1]. Taxol triggers apoptosis in ovarian cancer cells, and upregulates cytoprotective proteins and/or pathways that compromise its therapeutic efficacy [6,7]. Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells caspase-9 and caspase-3, indicating that the antiapoptosis signaling effect of GM3 synthase could be involved upstream of caspase-9 [15]. The roles of GM3 synthase in Taxol resistance or apoptosis triggered by this anticancer agent have not been delineated. In this project, we explored whether Taxol treatment increased the expression of GM3 synthase in SKOV3 human ovarian cancer cells, and whether forced expression affected the sensitivity of these cells to apoptosis, thereby altering the efficacy of Taxol therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
