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.
Highlights
Introduction iationsPlants have been an important source of new pharmacologically active compounds, with many blockbuster drugs being derived directly or indirectly from plants
The main objectives of our work were: (i) to compare three different cannabinoid extraction methods; (ii) to identify and quantify the compounds exhibiting anticancer activity on human pancreatic; and (iii) to study the mechanism of action for apoptosis induction in a pancreatic cancer line described for drug resistance
Purified water was obtained from a Merck Millipore Milli Q system (Millipore, Bedford, MA, USA), potassium persulfate, 2,20 -azo-bis(2-methylpropionamidine) dihydrochloride (AAPH), Gemcitabine and fluorescein were purchased from Merck-SigmaAldrich (Germany)
Summary
Plants have been an important source of new pharmacologically active compounds, with many blockbuster drugs being derived directly or indirectly from plants. As a means of discovering and making medicines, the contribution of plants to the treatment and prevention of disease remains enormous. Natural products will continue to be extremely important as sources of medicinal agents. Besides the natural products which have been found for direct medical application as medicinal entities, many others can serve as chemical models, or as models for the conception, synthesis, and semi-synthesis of new substances intended for the treatment of human diseases. The use of cannabinoids as anti-cancer therapeutics has been extensively studied. It can be concluded that they generally exert protective and beneficiary effects, inhibiting tumor growth and progression and restoring homeostasis. The clinical use of Licensee MDPI, Basel, Switzerland
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