Anti-prostate cancer activity and mechanism of the sesquiterpenoid lactone THA from Cyanthillium cinereum

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Abstract Purpose This study aims to evaluate the in vitro effect of 8α-tigloyloxyhirsutinolide-13-O-acetate (THA) on human prostate cancer cells and to examine its in vivo inhibitory effect on tumor growth in a mouse xenograft model. Methods In this study, the androgen-independent prostate cancer (AIPC) cell line PC-3 was employed. To investigate the effects of THA, we assessed cell proliferation, migration, invasion, apoptosis, and cell cycle distribution using MTT, wound healing, Transwell invasion, colony formation assays, Hoechst-33342 staining and flow cytometry. A mouse xenograft tumor model was established, and treatment groups received THA. The expression levels of p-STAT3, p-AKT, p-Erk1/2, CDK2, cyclin E1, MMP9, Bcl-2, Bax, and survivin were analyzed by Western blotting. Tumor formation and progression were evaluated by monitoring tumor volume. Results Our study showed that THA strongly inhibited cell growth and induced apoptosis, as well as caused cell cycle arrest at the S phase in PC-3 cells. THA also strongly suppressed cell migration and invasion, and decreased spheroid and colony formation. Animal experiment showed that THA inhibited the growth of PC-3 xenograft tumor in nude mice. Studies on mechanisms of actions showed that the potent anti-prostate cancer effects of THA were associated with inhibition of STAT3, AKT, and Erk1/2 pathways. Conclusion Our findings demonstrate that the potent anti-prostate cancer activity of THA is associated with inhibition of the STAT3, AKT, and Erk1/2 pathways. These data lend support to the further investigation of THA as a potential therapeutic agent against prostate cancer.
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Anti-prostate cancer activity and mechanism of the sesquiterpenoid lactone THA from Cyanthillium cinereum | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Anti-prostate cancer activity and mechanism of the sesquiterpenoid lactone THA from Cyanthillium cinereum Wenfeng Wang, Man Xiao, Peng Hong, Danyu Huang, Liting Liu, Xi Zheng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8798804/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose This study aims to evaluate the in vitro effect of 8α-tigloyloxyhirsutinolide-13-O-acetate (THA) on human prostate cancer cells and to examine its in vivo inhibitory effect on tumor growth in a mouse xenograft model. Methods In this study, the androgen-independent prostate cancer (AIPC) cell line PC-3 was employed. To investigate the effects of THA, we assessed cell proliferation, migration, invasion, apoptosis, and cell cycle distribution using MTT, wound healing, Transwell invasion, colony formation assays, Hoechst-33342 staining and flow cytometry. A mouse xenograft tumor model was established, and treatment groups received THA. The expression levels of p-STAT3, p-AKT, p-Erk1/2, CDK2, cyclin E1, MMP9, Bcl-2, Bax, and survivin were analyzed by Western blotting. Tumor formation and progression were evaluated by monitoring tumor volume. Results Our study showed that THA strongly inhibited cell growth and induced apoptosis, as well as caused cell cycle arrest at the S phase in PC-3 cells. THA also strongly suppressed cell migration and invasion, and decreased spheroid and colony formation. Animal experiment showed that THA inhibited the growth of PC-3 xenograft tumor in nude mice. Studies on mechanisms of actions showed that the potent anti-prostate cancer effects of THA were associated with inhibition of STAT3, AKT, and Erk1/2 pathways. Conclusion Our findings demonstrate that the potent anti-prostate cancer activity of THA is associated with inhibition of the STAT3, AKT, and Erk1/2 pathways. These data lend support to the further investigation of THA as a potential therapeutic agent against prostate cancer. Cyanthillium cinereum Prostate cancer Sesquiterpenoid lactone Apoptosis Xenograft tumor Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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