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Celastrus orbiculatus extract suppresses gastric cancer stem cells through the TGF-β/Smad signaling pathway

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Abstract

Cancer stem cells (CSCs) are the primary source of tumor recurrence and chemoresistance, which complicates tumor treatment and has a significant impact on poor patient prognosis. Therefore, the discovery of inhibitors that specifically target CSCs is warranted. Previous research has established that the TGF-β/Smad signaling pathway is critical for the maintenance of CSCs phenotype, thus facilitating CSCs transformation. In this regard, Celastrus orbiculatus ethyl acetate extract (COE) was shown to exert anticancer properties; however, its therapeutic impact on gastric cancer stem cells (GCSCs) remains unknown. We here demonstrate that COE displayed a strong inhibitory effect on GCSCs growth and CSCs markers. Moreover, COE was shown to efficiently inhibit the development of tumor spheres and accelerate GCSCs apoptosis. Mechanistically, we established that COE could suppress the stemness phenotype of GCSCs by inhibiting the activity of the TGF-β/Smad signaling pathway. To summarize, our data indicate that COE suppresses the malignant biological phenotype of GCSCs via the TGF-β/Smad signaling pathway. These findings shed new light on the anticancer properties of COE and suggest new strategies for the development of efficient GCSCs therapeutics.

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Funding

This study was financially supported by the National Natural Science Foundation of China (No. 82104946, No. 81773944, No. 81903906), Natural Science Foundation of Jiangsu Province (No. BK20210817); The Traditional Chinese Medicine Science and Technology Development Project of Jiangsu Province (Project code: QN202008); Yangzhou University International Academic Exchange Fund (YZUIAEF201902021); the China Postdoctoral Science Foundation (No.2018M642346); the China Postdoctoral Science Foundation (No.2017M611936) and the Jiangsu Postdoctoral Science Foundation (No.1701185B) to Li Tao.

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Authors and Affiliations

  1. TCM Department, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 136, Jiangyang Middle Road, Yangzhou, 225001, Jiangsu, People’s Republic of China

    Tengyang Ni, Zewen Chu, Miao Zhu, Yuanyuan Luo, Haibo Wang & Yanqing Liu

  2. Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Tengyang Ni, Zewen Chu, Miao Zhu, Yuanyuan Luo, Haibo Wang & Yanqing Liu

  3. Department of Pharmacy, College of Medicine, Yangzhou University, Yangzhou, 225001, Jiangsu, People’s Republic of China

    Li Tao, Yang Zhao & Mengying Lv

  4. Department of Physiology, School of Medicine, Showa University, Tokyo, 142, Japan

    Masataka Sunagawa

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  1. Tengyang Ni
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  2. Zewen Chu
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  3. Li Tao
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Ni, T., Chu, Z., Tao, L. et al. Celastrus orbiculatus extract suppresses gastric cancer stem cells through the TGF-β/Smad signaling pathway. J Nat Med 78, 100–113 (2024). https://doi.org/10.1007/s11418-023-01748-0

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