AUTHOR=Cheng Chien-Shan , Wu Yuan , Jin Jia-Bin , Xu Jia-Yue , Yang Pei-Wen , Zhu Wen-Hua , Zheng Lan , Chen Jing-Xian 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1284371

DOI=10.3389/fphar.2024.1284371

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold><italic>Cynanchum paniculatum</italic> (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.</p><p><bold>Aim:</bold> This study delves into the intricate anti-pancreatic cancer mechanisms of <italic>C. paniculatum</italic> (Bunge) Kitag. ex H.Hara aqueous extract (CPAE) by elucidating its role in apoptosis induction and the inhibition of invasion and migration.</p><p><bold>Methods:</bold> 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 <italic>in vivo</italic> anti-cancer potential.</p><p><bold>Results:</bold> 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. <italic>In vivo</italic> experiments underscored CPAE’s ability to inhibit tumor proliferation.</p><p><bold>Conclusion:</bold> This study illuminates the multifaceted anti-proliferative, pro-apoptotic, anti-invasive, and anti-migratory effects of CPAE, both <italic>in vitro</italic> and <italic>in vivo</italic>. 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.</p>