Novel hexahydrocannabinol analogs as potential anti-cancer agents inhibit cell proliferation and tumor angiogenesis

Title
Novel hexahydrocannabinol analogs as potential anti-cancer agents inhibit cell proliferation and tumor angiogenesis
Author(s)
김정애따파디네쉬이종숙허세웅이용록강건욱[강건욱]곽미경최한곤
Keywords
ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER CELLS; IN-VIVO; CHORIOALLANTOIC MEMBRANE; CANNABINOID RECEPTOR; DOWN-REGULATION; ACTIVATION; TAMOXIFEN; INVASION; SUPPRESSION
Issue Date
201101
Publisher
ELSEVIER SCIENCE BV
Citation
EUROPEAN JOURNAL OF PHARMACOLOGY, v.650, no.1, pp.64 - 71
Abstract
Both natural and synthetic cannabinoids have been shown to suppress the growth of tumor cells in culture and in animal models by affecting key signaling pathways including angiogenesis a pivotal step in tumor growth invasion and metastasis In our search for cannabinoid-like anticancer agents devoid of psychoactive side effects we synthesized and evaluated the anti-angiogenic effects of a novel series of hexahydrocannabinol analogs Among these two analogs LYR-7 [(9S)-3 669 tetramethyl-6a 7 8 9 10 10a-hexahydro-6H-benzo[c]chromen-1-ol] and LYR-8 (1 ((9S)-1-hydroxy 66 9-trimethyl-6a,7 89 10 10a hexahydro-6H benzo[c]chromen-2 yl)ethanone)) were selected based on their anti-angiogenic activity and lack of binding affinity for cannabinoid receptors Both LYR-7 and LYR-8 inhibited VEGF-Induced proliferation migration and capillary-like tube formation of HUVECs in a concentration dependent manner The inhibitory effect of the compounds on cell proliferation was more selective in endothelial cells than in breast cancer cells (MCF 7 and tamoxifen-resistant MCF-7) We also noted effective inhibition of VEGF-induced new blood vessel formation by the compounds in the in vivo chick chorioallantoic membrane (CAM) assay Furthermore both LYR analogs potently inhibited VEGF production and NF-kappa B transcriptional activity in cancer cells Additionally LYR 7 or LYR-8 strongly inhibited breast cancer cell induced angiogenesis and tumor growth Together these results suggest that novel synthetic hexahydrocannabinol analogs LYR-7 and LYR-8 inhibit tumor growth by targeting VEGF-mediated angiogenesis signaling in endothelial cells and suppressing VEGF production and cancer cell growth (C) 2010 Elsevier B V All rights reserved
URI
http://hdl.handle.net/YU.REPOSITORY/25799http://dx.doi.org/10.1016/j.ejphar.2010.09.073
ISSN
0014-2999
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약학대학 > 약학부 > Articles
공과대학 > 화학공학부 > Articles
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