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

  • Front Pharmacol. 2024 May 31:15:1284371. doi: 10.3389/fphar.2024.1284371.
Chien-Shan Cheng  #  1  2  3 ,  Yuan Wu  #  1 ,  Jia-Bin Jin  4  5 ,  Jia-Yue Xu  1 ,  Pei-Wen Yang  2  3 ,  Wen-Hua Zhu  1 ,  Lan Zheng  1 ,  Jing-Xian Chen  1
Affiliations
  • 1. Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China.
  • 2. Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 4. Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • # Contributed equally.
PMID: 38881872 DOI: 10.3389/fphar.2024.1284371
Abstract

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 C. 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 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 epithelial-mesenchymal 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; anti-invasion and anti-migration; apoptosis-induction; caspase-dependent apoptosis; epithelial-mesenchymal transition.