Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression.

Autor:	Nallathambi R; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel., Mazuz M; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel., Namdar D; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel., Shik M; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel.; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel., Namintzer D; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel.; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel., Vinayaka AC; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel., Ion A; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel., Faigenboim A; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel., Nasser A; The Interinstitutional Analytical Instrumentation Unit (IU), ARO, Volcani Center, Bet Dagan, Israel., Laish I; Department of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba, Israel., Konikoff FM; Department of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Koltai H; Agricultural Research Organization, Volcani Center, Bet Dagan, Israel.
Jazyk:	angličtina
Zdroj:	Cannabis and cannabinoid research [Cannabis Cannabinoid Res] 2018 Jun 01; Vol. 3 (1), pp. 120-135. Date of Electronic Publication: 2018 Jun 01 (Print Publication: 2018).
DOI:	10.1089/can.2018.0010
Abstrakt:	Introduction: Colorectal cancer remains the third most common cancer diagnosis and fourth leading cause of cancer-related mortality worldwide. Purified cannabinoids have been reported to prevent proliferation, metastasis, and induce apoptosis in a variety of cancer cell types. However, the active compounds from Cannabis sativa flowers and their interactions remain elusive. Research Aim: This study was aimed to specify the cytotoxic effect of C. sativa -derived extracts on colon cancer cells and adenomatous polyps by identification of active compound(s) and characterization of their interaction. Materials and Methods: Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography and gas chromatograph/mass spectrometry and their cytotoxic activity was determined using alamarBlue-based assay (Resazurin) and tetrazolium dye-based assay (XTT) on cancer and normal colon cell lines and on dysplastic adenomatous polyp cells. Annexin V Assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle, and RNA sequencing was used to determine gene expression. Results: The unheated cannabis extracts (C2F), fraction 7 (F7), and fraction 3 (F3) had cytotoxic activity on colon cancer cells, but reduced activity on normal colon cell lines. Moreover, synergistic interaction was found between F7 and F3 and the latter contains mainly cannabigerolic acid. The F7 and F7+F3 cytotoxic activity involved cell apoptosis and cell cycle arrest in S or G0/G1 phases, respectively. RNA profiling identified 2283 differentially expressed genes in F7+F3 treatment, among them genes related to the Wnt signaling pathway and apoptosis-related genes. Moreover, F7, F3, and F7+F3 treatments induced cell death of polyp cells. Conclusions: C. sativa compounds interact synergistically for cytotoxic activity against colon cancer cells and induce cell cycle arrest, apoptotic cell death, and distinct gene expression. F3, F7, and F7+F3 are also active on adenomatous polyps, suggesting possible future therapeutic value. Competing Interests: No competing financial interests exist.
Databáze:	MEDLINE
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