Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway
Wogonin, an active component derived from Scutellaria baicalensis, has shown anti-tumor activities in several malignancies. However, the roles of wogonin in RCC cells remain elusive. Here, we explored the effects of wogonin on RCC cells and the underlying mechanisms. We found that wogonin showed sig...
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| Format: | Article |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.01152/full |
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| author | Yong Wang Yong Wang Yong Wang Shouzhen Chen Shouzhen Chen Shuna Sun Guangyi Liu Lipeng Chen Lipeng Chen Yangyang Xia Yangyang Xia Jianfeng Cui Jianfeng Cui Wenfu Wang Wenfu Wang Xuewen Jiang Xuewen Jiang Lei Zhang Yaofeng Zhu Yongxin Zou Benkang Shi Benkang Shi |
| author_facet | Yong Wang Yong Wang Yong Wang Shouzhen Chen Shouzhen Chen Shuna Sun Guangyi Liu Lipeng Chen Lipeng Chen Yangyang Xia Yangyang Xia Jianfeng Cui Jianfeng Cui Wenfu Wang Wenfu Wang Xuewen Jiang Xuewen Jiang Lei Zhang Yaofeng Zhu Yongxin Zou Benkang Shi Benkang Shi |
| author_sort | Yong Wang |
| collection | DOAJ |
| description | Wogonin, an active component derived from Scutellaria baicalensis, has shown anti-tumor activities in several malignancies. However, the roles of wogonin in RCC cells remain elusive. Here, we explored the effects of wogonin on RCC cells and the underlying mechanisms. We found that wogonin showed significant cytotoxic effects against RCC cell lines 786-O and OS-RC-2, with much lower cytotoxic effects on human normal embryonic kidney cell line HEK-293 cells. Wogonin treatment dramatically inhibited the proliferation, migration, and invasion of RCC cells. We further showed that by inhibiting CDK4-RB pathway, wogonin transcriptionally down-regulated CDC6, disturbed DNA replication, induced DNA damage and apoptosis in RCC cells. Moreover, we found that the levels of p-RB, CDK4, and Cyclin D1 were up-regulated in sunitinib resistant 786-O, OS-RC-2, and TK-10 cells, and inhibition of CDK4 by palbociclib or wogonin effectively reversed the sunitinib resistance, indicating that the hyperactivation of CDK4-RB pathway may at least partially contribute to the resistance of RCC to sunitinib. Together, our findings demonstrate that wogonin could induce apoptosis and reverse sunitinib resistance of RCC cells via inhibiting CDK4-RB pathway, thus suggesting a potential therapeutic implication in the future management of RCC patients. |
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| language | English |
| last_indexed | 2024-12-12T08:54:42Z |
| publishDate | 2020-07-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-667947bfe28642028a7128837ca2bc1b2022-12-22T00:30:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-07-011110.3389/fphar.2020.01152547409Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB PathwayYong Wang0Yong Wang1Yong Wang2Shouzhen Chen3Shouzhen Chen4Shuna Sun5Guangyi Liu6Lipeng Chen7Lipeng Chen8Yangyang Xia9Yangyang Xia10Jianfeng Cui11Jianfeng Cui12Wenfu Wang13Wenfu Wang14Xuewen Jiang15Xuewen Jiang16Lei Zhang17Yaofeng Zhu18Yongxin Zou19Benkang Shi20Benkang Shi21Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology of Ministry of Education, Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, ChinaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, ChinaDepartment of Dermatology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, ChinaDepartment of Nephrology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, ChinaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, ChinaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, ChinaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, ChinaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, ChinaDepartment of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaThe Key Laboratory of Experimental Teratology of Ministry of Education, Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKey Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, ChinaWogonin, an active component derived from Scutellaria baicalensis, has shown anti-tumor activities in several malignancies. However, the roles of wogonin in RCC cells remain elusive. Here, we explored the effects of wogonin on RCC cells and the underlying mechanisms. We found that wogonin showed significant cytotoxic effects against RCC cell lines 786-O and OS-RC-2, with much lower cytotoxic effects on human normal embryonic kidney cell line HEK-293 cells. Wogonin treatment dramatically inhibited the proliferation, migration, and invasion of RCC cells. We further showed that by inhibiting CDK4-RB pathway, wogonin transcriptionally down-regulated CDC6, disturbed DNA replication, induced DNA damage and apoptosis in RCC cells. Moreover, we found that the levels of p-RB, CDK4, and Cyclin D1 were up-regulated in sunitinib resistant 786-O, OS-RC-2, and TK-10 cells, and inhibition of CDK4 by palbociclib or wogonin effectively reversed the sunitinib resistance, indicating that the hyperactivation of CDK4-RB pathway may at least partially contribute to the resistance of RCC to sunitinib. Together, our findings demonstrate that wogonin could induce apoptosis and reverse sunitinib resistance of RCC cells via inhibiting CDK4-RB pathway, thus suggesting a potential therapeutic implication in the future management of RCC patients.https://www.frontiersin.org/article/10.3389/fphar.2020.01152/fullwogoninRCCapoptosisCDK4-RBsunitinib |
| spellingShingle | Yong Wang Yong Wang Yong Wang Shouzhen Chen Shouzhen Chen Shuna Sun Guangyi Liu Lipeng Chen Lipeng Chen Yangyang Xia Yangyang Xia Jianfeng Cui Jianfeng Cui Wenfu Wang Wenfu Wang Xuewen Jiang Xuewen Jiang Lei Zhang Yaofeng Zhu Yongxin Zou Benkang Shi Benkang Shi Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway Frontiers in Pharmacology wogonin RCC apoptosis CDK4-RB sunitinib |
| title | Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway |
| title_full | Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway |
| title_fullStr | Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway |
| title_full_unstemmed | Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway |
| title_short | Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway |
| title_sort | wogonin induces apoptosis and reverses sunitinib resistance of renal cell carcinoma cells via inhibiting cdk4 rb pathway |
| topic | wogonin RCC apoptosis CDK4-RB sunitinib |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.01152/full |
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