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Cannabis sativa Extract Induces Apoptosis in Human Pancreatic 3D Cancer Models: Importance of Major Antioxidant Molecules Present Therein
Authors:Fathi Emhemmed  Minjie Zhao  Selvi Yorulmaz  Damien Steyer  Celine Leitao  Marion Alignan  Muriel Cerny  Alexandra Paillard  Franck Milone Delacourt  Diane Julien-David  Christian D Muller
Institution:1.IPHC, UMR 7178 CNRS, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France; (F.E.); (M.Z.); (S.Y.); (D.J.-D.);2.Twistaroma, 300 Bd Sébastien Brant, 67412 Illkirch, France; (D.S.); (C.L.);3.Laboratoire de Chimie Agro-Industrielle, LCA, Université de Toulouse, INRAE, 31400 Toulouse, France; (M.A.); (M.C.);4.DelleD/La Fleur, 1, rue Fleming, 49100 Angers, France; (A.P.); (F.M.D.)
Abstract:In recent years, interest in Cannabis sativa L. has been rising, as legislation is moving in the right direction. This plant has been known and used for thousands of years for its many active ingredients that lead to various therapeutic effects (pain management, anti-inflammatory, antioxidant, etc.). In this report, our objective was to optimize a method for the extraction of cannabinoids from a clone of Cannabis sativa L. #138 resulting from an agronomic test (LaFleur, Angers, FR). Thus, we wished to identify compounds with anticancer activity on human pancreatic tumor cell lines. Three static maceration procedures, with different extraction parameters, were compared based on their median inhibitory concentration (IC50) values and cannabinoid extraction yield. As CBD emerged as the molecule responsible for inducing apoptosis in the human pancreatic cancer cell line, a CBD-rich cannabis strain remains attractive for therapeutic applications. Additionally, while gemcitabine, a gold standard drug in the treatment of pancreatic cancer, only triggers cell cycle arrest in G0/G1, CBD also activates the cell signaling cascade to lead to programmed cell death. Our results emphasize the potential of natural products issued from medicinal hemp for pancreatic cancer therapy, as they lead to an accumulation of intracellular superoxide ions, affect the mitochondrial membrane potential, induce G1 cell cycle arrest, and ultimately drive the pancreatic cancer cell to lethal apoptosis.
Keywords:Cannabis sativa L    phytocannabinoids  phytochemicals  antioxidants  ROS  proapoptotic activity  caspase activation  TNF secretion  pancreatic cancer  human
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