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Anti‐angiogenic anti‐tumor activity of BJ‐1301, an α‐tocopherol analog (842.5)
Author(s) -
Banskota Suhrid,
Chandra Regmi Sushil,
Gautam Jaya,
Ku JinMo,
Nam Taegyu,
Jeong ByeongSeon,
Kim JungAe
Publication year - 2014
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.28.1_supplement.842.5
Subject(s) - angiogenesis , nadph oxidase , chorioallantoic membrane , chemistry , reactive oxygen species , vascular endothelial growth factor , ex vivo , in vivo , activator (genetics) , cancer research , pharmacology , in vitro , biochemistry , receptor , biology , vegf receptors , microbiology and biotechnology
Because reactive oxygen species (ROS) are generated upon activation of growth factor receptors including VEGFR, and direct application of ROS induces angiogenesis, many natural and synthetic antioxidants including vitamin E were examined and found to have a certain level of antiangiogenic activity. In the present study, we observed that a synthetic aminopyridinol antioxidant, BJ‐1301, inhibits vascular endothelial growth factor (VEGF)‐induced angiogenesis in the growing chick embryo chorioallantoic membrane (CAM), and tumor growth on CAM xenografted with A549 human lung cancer cells. The inhibitory effects of BJ‐1301 were more potent than those of natural and synthetic counterparts, α‐tocopherol (α‐TOH) and 2,2,5,7,8‐pentamethyl‐6‐hydroxychroman (PMC), as well as SU4312, a VEGF receptor tyrosine kinase inhibitor. BJ‐1301 also inhibited ROS generation by 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA), a direct activator of NADPH oxidase with greater potency than α‐TOH and PMC, and a similar potency trend was observed for their antiangiogenic activities in vivo as well as in vitro (BJ‐1301 > PMC > α‐TOH). Together, these results suggest that BJ‐1301, the aminopyridinol analog of α‐TOH, induces stronger inhibition of both angiogenesis and tumor growth than α‐TOH, PMC, or SU4312 by targeting NADPH oxidase. Grant Funding Source : This work was supported by the Basic Science Research Program through the National Research Foundati