An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a...
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Frontiers Media S.A.
2017-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00227/full |
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| author | Zhi-Ling Yu Zhi-Ling Yu Zhi-Ling Yu Tao Su Tao Su Tao Su Jing-Xuan Bai Ying-Jie Chen Xin-Ning Wang Xiu-Qiong Fu Xiu-Qiong Fu Xiu-Qiong Fu Ting Li Ting Li Ting Li Hui Guo Hui Guo Hui Guo Pei-Li Zhu Pei-Li Zhu Pei-Li Zhu Yue Wang |
| author_facet | Zhi-Ling Yu Zhi-Ling Yu Zhi-Ling Yu Tao Su Tao Su Tao Su Jing-Xuan Bai Ying-Jie Chen Xin-Ning Wang Xiu-Qiong Fu Xiu-Qiong Fu Xiu-Qiong Fu Ting Li Ting Li Ting Li Hui Guo Hui Guo Hui Guo Pei-Li Zhu Pei-Li Zhu Pei-Li Zhu Yue Wang |
| author_sort | Zhi-Ling Yu |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3. However, the anti-CRC mode and mechanism of action of AR have not been fully elucidated. Here, we investigated the involvement of STAT3 signaling in the anti-CRC effects of AR. Results showed that AR reduced cell viability, induced cell apoptosis, and suppressed cell migration and invasion in human HCT-116 and SW480 CRC cells. Mechanistic studies showed that AR potently suppressed STAT3 and Src phosphorylation, and inhibited STAT3 nuclear localization in cultured CRC cells. AR also downregulated the expression of STAT3 target genes Mcl-1, Bcl-xL, and MMP-2 that are involved in cell survival and mobility. Moreover, the cytotoxic effect of AR was diminished by overexpressing STAT3C, a persistent active variant of STAT3. In conclusion, AR exerted anti-CRC effects in vitro and these effects are at least in part attributed to the inhibition of STAT3 signaling. Our findings provide a molecular justification for the traditional use of AR in treating CRC, and a pharmacological basis for developing AR-derived modern anti-CRC agent(s). |
| first_indexed | 2024-12-16T16:25:22Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-16T16:25:22Z |
| publishDate | 2017-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-8258215051c448068054ba8925e42db92022-12-21T22:24:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-04-01810.3389/fphar.2017.00227258650An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In VitroZhi-Ling Yu0Zhi-Ling Yu1Zhi-Ling Yu2Tao Su3Tao Su4Tao Su5Jing-Xuan Bai6Ying-Jie Chen7Xin-Ning Wang8Xiu-Qiong Fu9Xiu-Qiong Fu10Xiu-Qiong Fu11Ting Li12Ting Li13Ting Li14Hui Guo15Hui Guo16Hui Guo17Pei-Li Zhu18Pei-Li Zhu19Pei-Li Zhu20Yue Wang21Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaCenter for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityHong Kong, ChinaHKBU Shenzhen Research Institute and Continuing EducationShenzhen, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaCenter for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityHong Kong, ChinaHKBU Shenzhen Research Institute and Continuing EducationShenzhen, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaCenter for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityHong Kong, ChinaHKBU Shenzhen Research Institute and Continuing EducationShenzhen, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaCenter for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityHong Kong, ChinaHKBU Shenzhen Research Institute and Continuing EducationShenzhen, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaCenter for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityHong Kong, ChinaHKBU Shenzhen Research Institute and Continuing EducationShenzhen, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaCenter for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityHong Kong, ChinaHKBU Shenzhen Research Institute and Continuing EducationShenzhen, ChinaConsun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist UniversityKowloon Tong, ChinaColorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3. However, the anti-CRC mode and mechanism of action of AR have not been fully elucidated. Here, we investigated the involvement of STAT3 signaling in the anti-CRC effects of AR. Results showed that AR reduced cell viability, induced cell apoptosis, and suppressed cell migration and invasion in human HCT-116 and SW480 CRC cells. Mechanistic studies showed that AR potently suppressed STAT3 and Src phosphorylation, and inhibited STAT3 nuclear localization in cultured CRC cells. AR also downregulated the expression of STAT3 target genes Mcl-1, Bcl-xL, and MMP-2 that are involved in cell survival and mobility. Moreover, the cytotoxic effect of AR was diminished by overexpressing STAT3C, a persistent active variant of STAT3. In conclusion, AR exerted anti-CRC effects in vitro and these effects are at least in part attributed to the inhibition of STAT3 signaling. Our findings provide a molecular justification for the traditional use of AR in treating CRC, and a pharmacological basis for developing AR-derived modern anti-CRC agent(s).http://journal.frontiersin.org/article/10.3389/fphar.2017.00227/fullAmpelopsis Radixcolorectal cancerSTAT3apoptosismigrationinvasion |
| spellingShingle | Zhi-Ling Yu Zhi-Ling Yu Zhi-Ling Yu Tao Su Tao Su Tao Su Jing-Xuan Bai Ying-Jie Chen Xin-Ning Wang Xiu-Qiong Fu Xiu-Qiong Fu Xiu-Qiong Fu Ting Li Ting Li Ting Li Hui Guo Hui Guo Hui Guo Pei-Li Zhu Pei-Li Zhu Pei-Li Zhu Yue Wang An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro Frontiers in Pharmacology Ampelopsis Radix colorectal cancer STAT3 apoptosis migration invasion |
| title | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
| title_full | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
| title_fullStr | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
| title_full_unstemmed | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
| title_short | An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro |
| title_sort | ethanolic extract of ampelopsis radix exerts anti colorectal cancer effects and potently inhibits stat3 signaling in vitro |
| topic | Ampelopsis Radix colorectal cancer STAT3 apoptosis migration invasion |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00227/full |
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