Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo

Sutapa Sinha, Krishnendu Pal, Ahmed Elkhanany, Shamit Dutta, Ying Cao, Gourish Mondal, Seethalakshmi Iyer, Veena Somasundaram, Fergus J Couch, Vijayalakshmi Shridhar, Resham Bhattacharya, Debabrata Mukhopadhyay, Priya Srinivas

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1201-1212
Number of pages12
JournalInternational Journal of Cancer
Volume132
Issue number5
DOIs
StatePublished - Mar 1 2013

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Ovarian Neoplasms
Carcinogenesis
Vascular Endothelial Growth Factor A
Cisplatin
Neoplasms
Angiogenesis Inhibitors
Drug Delivery Systems
plumbagin
Ear
Disease Progression
Endothelial Cells
Cell Proliferation
(1-hydroxy-1-methyl-3-phenylpropyl)-6,14-endo-ethenotetrahydrooripavine
Growth

Keywords

  • angiogenesis
  • cytotoxicity
  • ovarian cancer
  • plumbagin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sinha, S., Pal, K., Elkhanany, A., Dutta, S., Cao, Y., Mondal, G., ... Srinivas, P. (2013). Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo. International Journal of Cancer, 132(5), 1201-1212. https://doi.org/10.1002/ijc.27724

Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo. / Sinha, Sutapa; Pal, Krishnendu; Elkhanany, Ahmed; Dutta, Shamit; Cao, Ying; Mondal, Gourish; Iyer, Seethalakshmi; Somasundaram, Veena; Couch, Fergus J; Shridhar, Vijayalakshmi; Bhattacharya, Resham; Mukhopadhyay, Debabrata; Srinivas, Priya.

In: International Journal of Cancer, Vol. 132, No. 5, 01.03.2013, p. 1201-1212.

Research output: Contribution to journalArticle

Sinha, S, Pal, K, Elkhanany, A, Dutta, S, Cao, Y, Mondal, G, Iyer, S, Somasundaram, V, Couch, FJ, Shridhar, V, Bhattacharya, R, Mukhopadhyay, D & Srinivas, P 2013, 'Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo', International Journal of Cancer, vol. 132, no. 5, pp. 1201-1212. https://doi.org/10.1002/ijc.27724
Sinha, Sutapa ; Pal, Krishnendu ; Elkhanany, Ahmed ; Dutta, Shamit ; Cao, Ying ; Mondal, Gourish ; Iyer, Seethalakshmi ; Somasundaram, Veena ; Couch, Fergus J ; Shridhar, Vijayalakshmi ; Bhattacharya, Resham ; Mukhopadhyay, Debabrata ; Srinivas, Priya. / Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo. In: International Journal of Cancer. 2013 ; Vol. 132, No. 5. pp. 1201-1212.
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