Premium
Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo
Author(s) -
Sinha Sutapa,
Pal Krishnendu,
Elkhanany Ahmed,
Dutta Shamit,
Cao Ying,
Mondal Gourish,
Iyer Seethalakshmi,
Somasundaram Veena,
Couch Fergus J.,
Shridhar Viji,
Bhattacharya Resham,
Mukhopadhyay Debabrata,
Srinivas Priya
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27724
Subject(s) - plumbagin , angiogenesis , ovarian cancer , cancer research , cisplatin , cancer cell , carcinogenesis , cell growth , biology , vascular endothelial growth factor , neovascularization , cancer , pharmacology , medicine , chemotherapy , vegf receptors , biochemistry , genetics
Angiogenesis is a hallmark of tumor development and metastatic progression, and anti‐angiogenic drugs targeting the VEGF pathway have shown to decrease the disease progression in cancer patients. In this study, we have analyzed the anti‐proliferative and anti‐angiogenic property of plumbagin in cisplatin sensitive, BRCA2 deficient, PEO‐1 and cisplatin resistant, BRCA2 proficient PEO‐4 ovarian cancer cells. Both PEO‐1 and PEO‐4 ovarian cancer cells are sensitive to plumbagin irrespective of BRCA2 status in both normoxia and hypoxia. Importantly, plumbagin treatment effectively inhibits VEGF‐A and Glut‐1 in PEO‐1 and PEO‐4 ovarian cancer cells. We have also analyzed the p53 mutant, cisplatin resistant, and BRCA2 proficient OVCAR‐5 cells. Plumbagin challenge also restricts the VEGF induced pro‐angiogenic signaling in HUVECs and subsequently endothelial cell proliferation. In addition, we observe a significant effect on tumor regression among OVCAR‐5 tumor‐bearing mice treated with plumbagin, which is associated with significant inhibition of Ki67 and vWF expressions. Plumbagin also significantly reduces CD31 expression in an ear angiogenesis assay. Collectively, our studies indicate that plumbagin, as an anti‐cancer agent disrupts growth of ovarian cancer cells through the inhibition of proliferation as well as angiogenesis.