Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells

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dc.contributor.authorZhang, Peng
dc.contributor.authorLi, Hong
dc.contributor.authorYang, Bin
dc.contributor.authorYang, Fan
dc.contributor.authorZhang, Lin-Lin
dc.contributor.authorKong, Qing-You
dc.contributor.authorChen, Xiao-Yan
dc.contributor.authorWu, Mo-Li
dc.contributor.authorLiu, Jia
dc.date.accessioned2023-01-14T20:36:12Z
dc.date.available2023-01-14T20:36:12Z
dc.date.issued2014-05
dc.description.abstractCervical cancers/CCs are one of the commonest malignancies and the second leading cause of cancer-related death in women. Resveratrol inhibits CC cell growth but its molecular target(s) remains unclear. Since the signaling pathways mediated by STAT3, Notch1 and Wnt2 play beneficial roles in CC formation and progression, the effects of resveratrol on them in cervical adenocarcinoma (HeLa) and squamous cell carcinoma (SiHa) cells were analyzed. The biological significances of the above signaling for HeLa and SiHa cells were evaluated by treating the cells with STAT3, Wnt or Notch selective inhibitors. The frequencies of STAT3, Notch and Wnt activations in 68 cases of CC specimens and 38 non-cancerous cervical epithelia were examined by tissue microarray-based immunohistochemical staining. The results revealed that HeLa and SiHa cells treated by 100μM resveratrol showed extensive apoptosis, accompanied with suppression of STAT3, Notch and Wnt activations. Growth inhibition and apoptosis were found in HeLa and SiHa populations treated by AG490, a STAT3/JAK3 inhibitor but not the ones treated by Notch inhibitor L-685,458 or by Wnt inhibitor XAV-939. Immunohistochemical staining performed on the tissue microarrays showed that the frequencies of Notch1, Notch2, Hes1, Wnt2, Wnt5a and p-STAT3 detection as well as β-catenin nuclear translocation in CC samples were significantly higher than that of noncancerous group (p<0.01), while the expression rate of PIAS3 was remarkably low in cancer samples (p<0.01). Our results thus demonstrate that STAT3, Wnt and Notch signaling are frequently co-activated in human CC cells and specimens and resveratrol can concurrently inhibit those signaling activations and meanwhile lead cervical squamous cell carcinoma and adenocarcinoma cells to growth arrest and apoptosis. STAT3 signaling is more critical for CC cells and is the major target of resveratrol because selective inhibition of STAT3 rather than Wnt or Notch activation commits SiHa and HeLa cells to apoptosis.en_US
dc.identifier.citationZhang, P., Li, H., Yang, B., Yang, F., Zhang, L. L., Kong, Q. Y., Chen, X. Y., Wu, M. L., & Liu, J. (2014). Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells. Genes & cancer, 5(5-6), 154–164. https://doi.org/10.18632/genesandcancer.15en_US
dc.identifier.otherDOI: 10.18632/genesandcancer.15
dc.identifier.urihttps://hdl.handle.net/20.500.14041/5581
dc.language.isoen_USen_US
dc.publisherGenes & Canceren_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectCervical Cancersen_US
dc.subjectResveratrolen_US
dc.subjectMolecular Targeten_US
dc.subjectSignal Transduction Pathwaysen_US
dc.subjectSTAT3 Signalingen_US
dc.titleBiological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cellsen_US
dc.typeArticleen_US
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