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Hexahydrocannabinols, novel synthetic cannabinoid derivatives, suppress the tumor growth by inhibiting the VEGF secretion and angiogenesis
Author(s) -
Thapa Dinesh,
Lee Jong Suk,
Xia Likai,
Lee Yong Rok,
Kim JungAe
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.761.3
Subject(s) - angiogenesis , cannabinoid , secretion , vascular endothelial growth factor , in vivo , chemistry , pharmacology , cannabis sativa , cancer research , inflammation , microbiology and biotechnology , vegf receptors , biology , biochemistry , immunology , receptor , botany
Cannabinoids, the active components of Cannabis sativa L. have been shown to exert antiproliferative actions in wide spectrum of tumor cells. However, the specific mechanism and target for these processes remain poorly understood. In the present study we examined anticancer potentials of hexahydrocannabinols. The synthetic hexahydrocannabinols inhibited the vascular endothelial growth factor (VEGF)‐induced angiogenesis on in vivo chick chorioalantoic membrane (CAM) assay. In addition, hexahydrocannabinols suppressed VEGF‐stimulated proliferation, tube formation, and migration in a concentration‐dependent manner. In MCF‐7 cells, hexahydrocannabinols concentration‐dependently inhibited VEGF secretion. Furthermore, we found that the hexahydrocannabinols dose‐dependently inhibited tumor growth and tumor‐induced angiogenesis. In addition, these synthetic cannabinoids significantly inhibited the TPA‐induced NF‐ κ B activation, which is known to regulate many important genes for inflammation, angiogenesis, and tumor growth. Overall, these findings strongly suggest that synthetic hexahydrocannabinols may be the promising compounds for antitumor drug development.