Stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein respons

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Abstract Saturated fatty acids have an anti-proliferative effect on cells. However, there are multiple types of saturated fatty acids, and the effects of each one on cancer cells are not fully elucidated. Here, we explored the effects of palmitate and stearate, saturated fatty acids abundant in the biological systems, on cancer cells. We found that stearate, but not palmitate, had a broad anti-proliferative effect on cancer cell lines originating from multiple organs by causing DNA damage through the unfolded protein response pathway, while oleate mitigated this effect. Feeding an stearate-rich diet and simultaneously inhibiting stearoyl-CoA desaturase-1 activity induced an increase in stearate levels and a decrease in oleate levels in tissues, significantly inhibiting the growth of xenografted ovarian cancer cell lines and patient-derived xenografts. In conclusion, modification of the stearate and oleate dietary composition may have therapeutic significance for cancer.
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Stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein respons | 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 Article Stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein respons Koji Yamanoi, Ogura Jumpei, Eijiro Nakamura, Shiji Ito, Yuki Nakanishi, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3680771/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Saturated fatty acids have an anti-proliferative effect on cells. However, there are multiple types of saturated fatty acids, and the effects of each one on cancer cells are not fully elucidated. Here, we explored the effects of palmitate and stearate, saturated fatty acids abundant in the biological systems, on cancer cells. We found that stearate, but not palmitate, had a broad anti-proliferative effect on cancer cell lines originating from multiple organs by causing DNA damage through the unfolded protein response pathway, while oleate mitigated this effect. Feeding an stearate-rich diet and simultaneously inhibiting stearoyl-CoA desaturase-1 activity induced an increase in stearate levels and a decrease in oleate levels in tissues, significantly inhibiting the growth of xenografted ovarian cancer cell lines and patient-derived xenografts. In conclusion, modification of the stearate and oleate dietary composition may have therapeutic significance for cancer. Biological sciences/Cancer/Cancer metabolism Biological sciences/Chemical biology/Lipids/Fatty acids Biological sciences/Cell biology/Cell death/Apoptosis Biological sciences/Cancer/Cancer therapy/Cancer therapeutic resistance Biological sciences/Cancer/Gynaecological cancer/Ovarian cancer Full Text Additional Declarations Yes there is potential Competing Interest. Eijiro Nakamura has received research funding from Sumitomo Pharma CO., Ltd. Supplementary Files Supplementaryinformations.pdf Cite Share Download PDF Status: Under Review 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. 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