Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo.

Publication Type:

Journal Article

Source:

International journal of cancer. Journal international du cancer, Volume 132, Issue 5, p.1201-12 (2013)

Keywords:

Angiogenesis Inhibitorsdigestive disease, digestive deseases Animalsdigestive disease, digestive deseases Antigens, CD31digestive disease, digestive deseases Antineoplastic Agentsdigestive disease, digestive deseases Antineoplastic Agents, Phytogenicdigestive disease, digestive deseases BRCA2 Proteindigestive disease, digestive deseases Calciumdigestive disease, digestive deseases Cell Line, Tumordigestive disease, digestive deseases Cell Proliferationdigestive disease, digestive deseases Cell Transformation, Neoplasticdigestive disease, digestive deseases Cisplatindigestive disease, digestive deseases Endothelial Cellsdigestive disease, digestive deseases Femaledigestive disease, digestive deseases Glucose Transporter Type 1digestive disease, digestive deseases Humansdigestive disease, digestive deseases Ki-67 Antigendigestive disease, digestive deseases Micedigestive disease, digestive deseases Mice, SCIDdigestive disease, digestive deseases Naphthoquinonesdigestive disease, digestive deseases Neovascularization, Pathologicdigestive disease, digestive deseases Ovarian Neoplasmsdigestive disease, digestive deseases Random Allocationdigestive disease, digestive deseases Tumor Suppressor Protein p53digestive disease, digestive deseases Vascular Endothelial Growth Factor Adigestive disease, digestive deseases Xenograft Model Antitumor Assays

Abstract:

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.