A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response
Abstract Fatty acids are known to have significant effects on the properties of cancer cells. Therefore, these compounds have been incorporated into therapeutic strategies. However, few studies have examined the effects of individual fatty acids and their interactions in depth. This study analyzed t...
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| Format: | Article |
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Nature Publishing Group
2024-12-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01356-2 |
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| author | Jumpei Ogura Koji Yamanoi Kentaro Ishida Eijiro Nakamura Shinji Ito Naoki Aoyama Yuki Nakanishi Toshi Menju Kosuke Kawaguchi Yuko Hosoe Mana Taki Ryusuke Murakami Ken Yamaguchi Junzo Hamanishi Masaki Mandai |
| author_facet | Jumpei Ogura Koji Yamanoi Kentaro Ishida Eijiro Nakamura Shinji Ito Naoki Aoyama Yuki Nakanishi Toshi Menju Kosuke Kawaguchi Yuko Hosoe Mana Taki Ryusuke Murakami Ken Yamaguchi Junzo Hamanishi Masaki Mandai |
| author_sort | Jumpei Ogura |
| collection | DOAJ |
| description | Abstract Fatty acids are known to have significant effects on the properties of cancer cells. Therefore, these compounds have been incorporated into therapeutic strategies. However, few studies have examined the effects of individual fatty acids and their interactions in depth. This study analyzed the effects of various fatty acids on cancer cells and revealed that stearic acid, an abundant saturated fatty acid, had a stronger inhibitory effect on cell growth than did palmitic acid, which is also an abundant saturated fatty acid, by inducing DNA damage and apoptosis through the unfolded protein response (UPR) pathway. Intriguingly, the negative effects of stearate were reduced by the presence of oleate, a different type of abundant fatty acid. We combined a stearate-rich diet with the inhibition of stearoyl-CoA desaturase-1 to explore the impact of diet on tumor growth. This intervention significantly reduced tumor growth in both ovarian cancer models and patient-derived xenografts (PDXs), including those with chemotherapy resistance, notably by increasing stearate levels while reducing oleate levels within the tumors. Conversely, the negative effects of a stearate-rich diet were mitigated by an oleate-rich diet. This study revealed that dietary stearate can directly inhibit tumor growth through mechanisms involving DNA damage and apoptosis mediated by the UPR pathway. These results suggest that dietary interventions, which increase stearic acid levels while decreasing oleic acid levels, may be promising therapeutic strategies for cancer treatment. These results could lead to the development of new cancer treatment strategies. |
| format | Article |
| id | doaj-art-e944aa1ad558412d806b004d6d514d4c |
| institution | DOAJ |
| issn | 2092-6413 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-e944aa1ad558412d806b004d6d514d4c2025-08-20T02:39:50ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132024-12-0156122659267210.1038/s12276-024-01356-2A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein responseJumpei Ogura0Koji Yamanoi1Kentaro Ishida2Eijiro Nakamura3Shinji Ito4Naoki Aoyama5Yuki Nakanishi6Toshi Menju7Kosuke Kawaguchi8Yuko Hosoe9Mana Taki10Ryusuke Murakami11Ken Yamaguchi12Junzo Hamanishi13Masaki Mandai14Department of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineDepartment of Urology and Retroperitoneal Surgery, National Cancer Center HospitalMedical Research Support Center, Kyoto University Graduate School of MedicineDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of MedicineDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of MedicineDepartment of Thoracic Surgery, Kyoto University Graduate School of MedicineDepartment of Breast Surgery, Kyoto University Graduate School of MedicineDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineDepartment of Gynecology and Obstetrics, Kyoto University Graduate School of MedicineAbstract Fatty acids are known to have significant effects on the properties of cancer cells. Therefore, these compounds have been incorporated into therapeutic strategies. However, few studies have examined the effects of individual fatty acids and their interactions in depth. This study analyzed the effects of various fatty acids on cancer cells and revealed that stearic acid, an abundant saturated fatty acid, had a stronger inhibitory effect on cell growth than did palmitic acid, which is also an abundant saturated fatty acid, by inducing DNA damage and apoptosis through the unfolded protein response (UPR) pathway. Intriguingly, the negative effects of stearate were reduced by the presence of oleate, a different type of abundant fatty acid. We combined a stearate-rich diet with the inhibition of stearoyl-CoA desaturase-1 to explore the impact of diet on tumor growth. This intervention significantly reduced tumor growth in both ovarian cancer models and patient-derived xenografts (PDXs), including those with chemotherapy resistance, notably by increasing stearate levels while reducing oleate levels within the tumors. Conversely, the negative effects of a stearate-rich diet were mitigated by an oleate-rich diet. This study revealed that dietary stearate can directly inhibit tumor growth through mechanisms involving DNA damage and apoptosis mediated by the UPR pathway. These results suggest that dietary interventions, which increase stearic acid levels while decreasing oleic acid levels, may be promising therapeutic strategies for cancer treatment. These results could lead to the development of new cancer treatment strategies.https://doi.org/10.1038/s12276-024-01356-2 |
| spellingShingle | Jumpei Ogura Koji Yamanoi Kentaro Ishida Eijiro Nakamura Shinji Ito Naoki Aoyama Yuki Nakanishi Toshi Menju Kosuke Kawaguchi Yuko Hosoe Mana Taki Ryusuke Murakami Ken Yamaguchi Junzo Hamanishi Masaki Mandai A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response Experimental and Molecular Medicine |
| title | A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response |
| title_full | A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response |
| title_fullStr | A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response |
| title_full_unstemmed | A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response |
| title_short | A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response |
| title_sort | stearate rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response |
| url | https://doi.org/10.1038/s12276-024-01356-2 |
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