Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer
Gastric cancer is a common type of malignant tumor with a relatively poor prognosis and presents a serious threat to global health. Signal Transducer and Activator of Transcription-3 (STAT3) has been strongly implicated in many cancers, and its constitutive activation promotes growth, angiogenesis,...
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| Format: | Article |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.870367/full |
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| author | Dehua Yu Dehua Yu Simin Qi Simin Qi Xiaoqing Guan Wenkai Yu Wenkai Yu Xuefei Yu Maohua Cai Maohua Cai Qinglin Li Weiyi Wang Weidong Zhang Weidong Zhang Weidong Zhang Jiang-Jiang Qin Jiang-Jiang Qin |
| author_facet | Dehua Yu Dehua Yu Simin Qi Simin Qi Xiaoqing Guan Wenkai Yu Wenkai Yu Xuefei Yu Maohua Cai Maohua Cai Qinglin Li Weiyi Wang Weidong Zhang Weidong Zhang Weidong Zhang Jiang-Jiang Qin Jiang-Jiang Qin |
| author_sort | Dehua Yu |
| collection | DOAJ |
| description | Gastric cancer is a common type of malignant tumor with a relatively poor prognosis and presents a serious threat to global health. Signal Transducer and Activator of Transcription-3 (STAT3) has been strongly implicated in many cancers, and its constitutive activation promotes growth, angiogenesis, inflammation, and immune evasion. Therefore, considerable efforts have been put into developing effective and safe STAT3 inhibitors. In this study, we performed a virtual screening by molecular docking and found that terphenyllin, a marine-derived natural product, directly interacted with STAT3. We further found that terphenyllin inhibited the phosphorylation and activation of STAT3 and decreased the protein levels of STAT3-dependent target genes, including c-Myc and Cyclin D1. Subsequently, we demonstrated that terphenyllin exerted its potent anticancer efficacy against gastric cancer in vitro and in vivo. Terphenyllin concentration-dependently inhibited growth, proliferation, and colony formation and induced cell cycle arrest and apoptosis of gastric cancer cells in vitro. Moreover, terphenyllin treatment suppressed the tumor growth and metastasis in a gastric cancer orthotopic mouse model without notable toxicity in vivo. Taken together, our results indicated that terphenyllin exerts its anticancer activity by inhibiting the STAT3 signaling pathway and may serve as a potent STAT3 inhibitor for gastric cancer treatment. |
| first_indexed | 2024-12-13T08:57:57Z |
| format | Article |
| id | doaj.art-a8386e640ca043f1a8d1701330c05837 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T08:57:57Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-a8386e640ca043f1a8d1701330c058372022-12-21T23:53:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.870367870367Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric CancerDehua Yu0Dehua Yu1Simin Qi2Simin Qi3Xiaoqing Guan4Wenkai Yu5Wenkai Yu6Xuefei Yu7Maohua Cai8Maohua Cai9Qinglin Li10Weiyi Wang11Weidong Zhang12Weidong Zhang13Weidong Zhang14Jiang-Jiang Qin15Jiang-Jiang Qin16College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaKey Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaInstitute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Pharmacy, Second Military Medical University, Shanghai, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaGastric cancer is a common type of malignant tumor with a relatively poor prognosis and presents a serious threat to global health. Signal Transducer and Activator of Transcription-3 (STAT3) has been strongly implicated in many cancers, and its constitutive activation promotes growth, angiogenesis, inflammation, and immune evasion. Therefore, considerable efforts have been put into developing effective and safe STAT3 inhibitors. In this study, we performed a virtual screening by molecular docking and found that terphenyllin, a marine-derived natural product, directly interacted with STAT3. We further found that terphenyllin inhibited the phosphorylation and activation of STAT3 and decreased the protein levels of STAT3-dependent target genes, including c-Myc and Cyclin D1. Subsequently, we demonstrated that terphenyllin exerted its potent anticancer efficacy against gastric cancer in vitro and in vivo. Terphenyllin concentration-dependently inhibited growth, proliferation, and colony formation and induced cell cycle arrest and apoptosis of gastric cancer cells in vitro. Moreover, terphenyllin treatment suppressed the tumor growth and metastasis in a gastric cancer orthotopic mouse model without notable toxicity in vivo. Taken together, our results indicated that terphenyllin exerts its anticancer activity by inhibiting the STAT3 signaling pathway and may serve as a potent STAT3 inhibitor for gastric cancer treatment.https://www.frontiersin.org/articles/10.3389/fphar.2022.870367/fullSTAT3inhibitornatural productgastric cancerterphenyllin |
| spellingShingle | Dehua Yu Dehua Yu Simin Qi Simin Qi Xiaoqing Guan Wenkai Yu Wenkai Yu Xuefei Yu Maohua Cai Maohua Cai Qinglin Li Weiyi Wang Weidong Zhang Weidong Zhang Weidong Zhang Jiang-Jiang Qin Jiang-Jiang Qin Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer Frontiers in Pharmacology STAT3 inhibitor natural product gastric cancer terphenyllin |
| title | Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer |
| title_full | Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer |
| title_fullStr | Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer |
| title_full_unstemmed | Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer |
| title_short | Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer |
| title_sort | inhibition of stat3 signaling pathway by terphenyllin suppresses growth and metastasis of gastric cancer |
| topic | STAT3 inhibitor natural product gastric cancer terphenyllin |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.870367/full |
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