Effect of the isoflavone corylin from cullen corylifolium on colorectal cancer growth,by targeting the STAT3 signaling pathway |
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| Affiliation: | 1. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China;2. The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China;3. The Second Affiliated Hospital and Yuying Children''s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China;4. The Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, China;5. Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China;1. Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Republic of Korea;2. GENENCELL Co., Ltd., Suite #2201, UTOWER, 120, Heungdeokjungang-ro, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea;1. College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China;2. Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China;3. The First Affiliation Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China;4. Huzhou Institute for Food and Drug Control, Huzhou 313000, China;5. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China;6. Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA;1. Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China;2. School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China |
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| Abstract: | BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide. Corylin is an isoflavone extracted from Cullen corylifolium (L.) Medik., which is widely used anti-inflammatory and anticancer in Asian countries. Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and development of CRC.PurposeTo analyze the antitumor activity of corylin in CRC and to elucidate its molecular mechanisms of action.MethodsThe human CRC cell lines HCT116, RKO, and SW480 and immunodeficient mice were used as models to study the antitumor effect of corylin. The potent anti-proliferative, anti-migration and proapoptotic effects of corylin were observed by cell viability, colony formation assays, wound-healing migration assay, and cell apoptosis assay. Immunostaining analysis and western blot analysis revealed inhibition of the STAT3 signaling axis.ResultsWe found that corylin could significantly reduce the viability and stimulate apoptosis in human CRC cells in a dose-dependent manner. Corylin decreased the expression levels of P-STAT3 and STAT3 target proteins, such as myeloid cell leukemia-1(MCL-1), Survivin, VEGF and B-cell lymphoma 2 (BCL-2). It also upregulated the expression levels of the proapoptotic proteins BCL-2-associated X protein (BAX) and Cl-caspase 3. Moreover, corylin reduced the nuclear localization of STAT3. Furthermore, corylin inhibited the growth of the tumor in CRC mouse models.ConclusionsOur findings provide convincing results that could support the role of corylin in the treatment of CRC through inhibiting the STAT3 pathway. It is conceivable that corylin should be further explored as a unique STAT3 inhibitor in antitumor therapy. |
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