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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1284371
This article is part of the Research Topic Treating Gastrointestinal Diseases with Traditional Medicine: Methodologies, Clinical Applications, and Mechanism of Action View all 9 articles

Cynanchum paniculatum (Bunge) Kitag. ex H.Hara inhibits pancreatic cancer progression by inducing Caspase-dependent apoptosis and suppressing TGF-β-mediated epithelial-mesenchymal transition

Provisionally accepted
  • 1 Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Beijing, China
  • 2 Shanghai Cancer Center, Fudan University, Shanghai, Shanghai Municipality, China

The final, formatted version of the article will be published soon.

    Background: Cynanchum paniculatum (Bunge) Kitag. ex H.Hara, a member of the Asclepiadaceae family, has a rich history as a traditional Chinese medicinal plant used to treat digestive disorders. However, its potential anti-cancer effects in pancreatic cancer remain largely unexplored.Aim: This study delves into the intricate anti-pancreatic cancer mechanisms of Cynanchum paniculatum (Bunge) Kitag. ex H.Hara aqueous extract (CPAE) by elucidating its role in apoptosis induction and the inhibition of invasion and migration. Methods: A comprehensive set of methodologies was employed to assess CPAE's impact, including cell viability analyses using MTT and colony formation assays, flow cytometry for cell cycle distribution and apoptosis assessment, scratch-wound and Matrigel invasion assays for migration and invasion capabilities, and immunoblotting to to measure the expression levels of key proteins involved in apoptosis and metastasis. Additionally, a murine xenograft model was established to investigate CPAE's in vivo anti-cancer potential.Results: CPAE exhibited time-and dose-dependent suppression of proliferation and colony formation in pancreatic cancer cells. Notably, CPAE induced apoptosis and G2/M phase arrest, effectively activating the caspase-dependent PARP pathway. At non-cytotoxic doses, CPAE significantly curtailed the metastatic abilities of pancreatic cells, effectively suppressing epithelialmesenchymal transition (EMT) and downregulating the TGF-β1/Smad2/3 pathway. In vivo experiments underscored CPAE's ability to inhibit tumor proliferation.Conclusion: This study illuminates the multifaceted anti-proliferative, pro-apoptotic, anti-invasive, and anti-migratory effects of CPAE, both in vitro and in vivo. CPAE emerges as a promising herbal medicine for pancreatic cancer treatment, with its potential mediated through apoptosis induction via the caspase-dependent PARP pathway and MET suppression via the TGF-β1/Smad2/3 signaling pathway at non-cytotoxic doses. These findings advocate for further exploration of CPAE's therapeutic potential in pancreatic cancer.

    Keywords: Cynanchum paniculatum (Bunge) Kitag. ex H.Hara, apoptosis-induction, anti-invasion and anti-migration, Caspase-dependent apoptosis, Epithelial-Mesenchymal Transition

    Received: 28 Aug 2023; Accepted: 30 Apr 2024.

    Copyright: © 2024 Cheng, Wu, Jin, Xu, Yang, Zhu, Zheng and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jingxian Chen, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.