Human β-galactoside α-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity

Huang, Su; Day, Travis W.; Choi, Mi Ran; Safa, Ahmad R.

doi:10.1007/s11010-009-0147-9

Cited by 24 publications

(15 citation statements)

References 43 publications

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“…We have found that Taxol at 100 – 500 nM induces robust apoptosis in cell lines from different types of cancer [22]. As shown in Figure 1(a), the annexin V binding assay revealed that Taxol at 100 nM induced early apop tosis in 28% of SKOV3 cells, and RT-PCR analysis showed that while SKOV3 cells express little GM3 synthase at the mRNA level, it was significantly increased after Taxol treatment (Figure 1(b)).…”

Section: Resultsmentioning

confidence: 96%

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Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells

Huang

Bijangi-Vishehsaraei

Saadatzadeh³

et al. 2012

JCT

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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.

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Section: Resultsmentioning

confidence: 96%

“…Our previous results showed that Taxol-induced apoptosis in SKOV3 ovarian cancer cells is associated with caspase-8, -9, and -3 activation in these cells [22]. Despite cytoreductive surgery and primary chemotherapy, advanced epithelial ovarian cancer is a highly lethal malignancy [23].…”

Section: Discussionmentioning

confidence: 99%

Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells

Huang

Bijangi-Vishehsaraei

Saadatzadeh³

et al. 2012

JCT

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“…22 Sialyltransferases participates of many biological processes, including cell-cell communication, cell-matrix interaction, adhesion, and protein targeting. 23 …”

Section: Discussionmentioning

confidence: 99%

Expression patterns of α2,3-Sialyltransferase I and α2,6-Sialyltransferase I in human cutaneous epithelial lesions

Ferreira¹,

Vasconcelos²,

Silva³

et al. 2013

Eur J Histochem

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Skin tumors have become one of the most common cancers in the world and their carcinogenesis is frequently associated with altered glycosylation patterns. The aberrant sialylation, a type of glycosylation, can mediate pathophysiological key events during various stages of tumor progression, including invasion and metastasis. Sialyltransferases play a key role in a variety of biological processes, including cell-cell communication, cell-matrix interaction, adhesion, and protein targeting. In this study, it was evaluated the expression of ST3Gal I and ST6Gal I in cutaneous epithelial lesions that include actinic keratosis (n=15), keratoacanthoma (n=9), squamous cell carcinoma (n=22) and basal cell carcinoma (n=28) in order to evaluate if sialyltransferases expression is different in premalignant and in malignant tumors. The expression of ST3Gal I was observed in actinic keratosis (53%), keratoacanthoma (78%), squamous cell carcinoma (73%) and basal cell carcinoma (32%) with statistic differences between basal cell carcinoma and keratoacanthoma (P=0.0239) and basal cell carcinoma and squamous cell carcinoma (P=0.0096); for ST6Gal I, cytoplasmic expression was noted in actinic keratosis (40%), heterogeneous and cytoplasmic expression was noted in keratoacanthoma (67%), squamous cell carcinoma (41%) and basal cell carcinoma (7%) with statistic differences between basal cell carcinoma and squamous cell carcinoma (P=0.0061) and basal cell carcinoma and keratoacanthoma (P=0.0008). In summary, our results showed that the high expression of ST3Gal I and ST6Gal I, in skin tumors, is associated with tumors with greater potential for invasion and metastasis, as in the case of squamous cell carcinoma, and this may be related to their behavior.

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“…The ST family consists of three subfamilies with 20 anabolic enzymes [12], namely, α2,3-sialyltransferases that mediate the transfer of sialic acid with an α2,3-linkage to terminal Gal residues (ST3GalI-VI) and α2,6-sialyltransferases that mediate the transfer of sialic acid with an α2,6-linkage to terminal Gal (ST6GalI-II) or GalNAc residues (ST6GalNAcI-VI) [13, 14]. The link between the ST family and EOC was reported previously by few studies [15–17]. For example, Christie et al reported that sialylation of β1 integrins mediated by ST6Gal-I altered the adhesion and migration characteristics of ovarian cancer cells through the extracellular matrix leading to peritoneal metastasis [17].…”

Section: Introductionmentioning

confidence: 95%

α2,3-sialyltransferase type I regulates migration and peritoneal dissemination of ovarian cancer cells

et al. 2017

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Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecologic cancers due to advanced stage presentation, peritoneal dissemination, and refractory ascites at diagnosis. We investigated the role of α2,3-sialyltransferase type I (ST3GalI) by analyzing human ovarian cancer datasets and human EOC tissue arrays. We found that high expression of ST3GalI was associated with advanced stage EOC. Transwell migration and cell invasion assays showed that high ST3GalI expression enhanced migration of EOC cells. We also observed that there was a linear relation between ST3GalI expression and epidermal growth factor receptor (EGFR) signaling in EOC patients, and that high ST3GalI expression blocked the effect of EGFR inhibitors. Co-Immunoprecipitation experiments demonstrated that ST3GalI and EGFR were present in the same protein complex. Inhibition of ST3GalI using a competitive inhibitor, Soyasaponin I (SsaI), inhibited tumor cell migration and dissemination in the in vivo mouse model with transplanted MOSEC cells. Further, SsaI synergistically enhanced the anti-tumor effects of EGFR inhibitor on EOC cells. Our study demonstrates that ST3GalI regulates ovarian cancer cell migration and peritoneal dissemination via EGFR signaling. This suggests α2,3-linked sialylation inhibitors in combination with EGFR inhibitors could be effective agents for the treatment of EOC.

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Human β-galactoside α-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity

Cited by 24 publications

References 43 publications

Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells

Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells

Expression patterns of α2,3-Sialyltransferase I and α2,6-Sialyltransferase I in human cutaneous epithelial lesions

α2,3-sialyltransferase type I regulates migration and peritoneal dissemination of ovarian cancer cells

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