The tobacco cembranoid (1S,2E,4S,7E,11E)-2,7,11-cembratriene-4,6-diol as a novel angiogenesis inhibitory lead for the control of breast malignancies.
(1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) and its 4-epi-analog (2) are diterpene precursors of the key flavor components in most Nicotiana (tobacco) species that purposely degraded during commercial tobacco fermentation. Angiogenesis, recruitment of new blood vessels, is important for tumor growth, survival and metastasis that can be targeted to control cancer. This study shows evidences and potential of the cembranoid 1 as a potent angiogenesis modulator through targeting VEGFR2. In silico study suggested favorable docking scores and binding affinity of 1 at the ATP binding pocket of VEGFR2. The binding mode of 1 was parallel to the standard FDA-approved antiangiogenic drug sunitinib (4). In vitro, cembranoid 1 significantly reduced the activated VEGFR2 levels in multiple breast cancer cell lines. Intraperitoneal 40mg/kg, 3X/week treatment of 1 significantly reduced the MDA-MB-231 cells breast tumor size in mice. Immunohistochemistry and Western blotting analysis of the treated mice tumors showed significant downregulation of the vasculogenesis marker CD31 and suppressed activated VEGFR2-paxillin-FAK pathway. Matrigel study in Swiss albino mice showed similar trend. The tobacco cembranoid 1 is a potential antiangiogenic lead useful for future use to control breast malignancies.
['Hailat|Mohammad M|MM|', 'Ebrahim|Hassan Y|HY|', 'Mohyeldin|Mohamed M|MM|', 'Goda|Amira A|AA|', 'Siddique|Abu Bakar|AB|', 'El Sayed|Khalid A|KA|']
D020533:Angiogenesis Inhibitors D000818:Animals D045744:Cell Line, Tumor D004224:Diterpenes D005260:Female D006801:Humans D051379:Mice D014026:Tobacco D023041:Xenograft Model Antitumor Assays
Tobacco cembranoids Angiogenesis Breast cancer FAK Paxillin VEGFR(2)