Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer
ABSTRACTEmerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-t...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Cancer Biology & Therapy |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2024.2325130 |
| _version_ | 1797265984700022784 |
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| author | Jianqing Qiu Ziyi Zhao Hongyan Suo Sarah E. Paraghamian Gabrielle M. Hawkins Wenchuan Sun Xin Zhang Tianran Hao Beor Deng Xiaochang Shen Chunxiao Zhou Victoria Bae-Jump |
| author_facet | Jianqing Qiu Ziyi Zhao Hongyan Suo Sarah E. Paraghamian Gabrielle M. Hawkins Wenchuan Sun Xin Zhang Tianran Hao Beor Deng Xiaochang Shen Chunxiao Zhou Victoria Bae-Jump |
| author_sort | Jianqing Qiu |
| collection | DOAJ |
| description | ABSTRACTEmerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of Lkb1fl/flp53fl/fl transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the Lkb1fl/flp53fl/fl mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer. |
| first_indexed | 2024-04-25T00:53:29Z |
| format | Article |
| id | doaj.art-0a883326542640ba9fd25fa4fea02307 |
| institution | Directory Open Access Journal |
| issn | 1538-4047 1555-8576 |
| language | English |
| last_indexed | 2024-04-25T00:53:29Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj.art-0a883326542640ba9fd25fa4fea023072024-03-11T12:12:41ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2325130Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancerJianqing Qiu0Ziyi Zhao1Hongyan Suo2Sarah E. Paraghamian3Gabrielle M. Hawkins4Wenchuan Sun5Xin Zhang6Tianran Hao7Beor Deng8Xiaochang Shen9Chunxiao Zhou10Victoria Bae-Jump11Department of Obstetrics and Gynecology, the Second Hospital of Shandong University, Jinan, PR, ChinaDivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAABSTRACTEmerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of Lkb1fl/flp53fl/fl transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the Lkb1fl/flp53fl/fl mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer.https://www.tandfonline.com/doi/10.1080/15384047.2024.2325130Linoleic acidendometrial cancerapoptosiscell cycleinvasioncellular stress |
| spellingShingle | Jianqing Qiu Ziyi Zhao Hongyan Suo Sarah E. Paraghamian Gabrielle M. Hawkins Wenchuan Sun Xin Zhang Tianran Hao Beor Deng Xiaochang Shen Chunxiao Zhou Victoria Bae-Jump Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer Cancer Biology & Therapy Linoleic acid endometrial cancer apoptosis cell cycle invasion cellular stress |
| title | Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer |
| title_full | Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer |
| title_fullStr | Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer |
| title_full_unstemmed | Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer |
| title_short | Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer |
| title_sort | linoleic acid exhibits anti proliferative and anti invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer |
| topic | Linoleic acid endometrial cancer apoptosis cell cycle invasion cellular stress |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2024.2325130 |
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