Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells

  • Authors: Kyu Kwang Kim, Ajay P. Singh, Rakesh K. Singh, Angelica DeMartino, Laurent Brard, Nicholi Vorsa, Thilo S. Lange, Richard G. Moore
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  • Published online on: Monday, September 12, 2011
  • Pages: 227-235
  • DOI: 10.3892/ijo.2011.1198

Abstract

Cranberry extracts may provide beneficial health effects in the treatment of various diseases, including cancer. However, the underlying molecular mechanisms of antineoplastic properties are not understood. We report the effect of a proanthocyanidin (PAC)-rich isolate from cranberry (PAC-1) as a therapeutic agent with dual activity to target both ovarian cancer viability and angiogenesis in vitro. PAC-1 treatment of chemotherapy-resistant SKOV-3 cells blocked cell cycle progression through the G2/M phase, increased the generation of reactive oxygen species (ROS), and induced apoptosis through activation of intrinsic and extrinsic pathway components. Cytotoxicity of PAC-1 was partially based on ROS generation and could be blocked by co-treatment with antioxidant glutathione. PAC-1 reduced the cell viability of both SKOV-3 ovarian cancer cells and HUVEC endothelial cells in a dose-dependent manner and blocked the activation of the pro-survival factor AKT. Furthermore, PAC-1 blocked vascular endothelial growth factor (VEGF)-stimulated receptor phosphorylation in endothelial cells, which correlated with the inhibition of endothelial tube formation in vitro. Our findings suggest that PAC-1 exerts potent anticancer and anti-angiogenic properties and that highly purified PAC from cranberry can be further developed to treat ovarian cancer in combinational or single-agent therapy.
Journal Cover

January 2012
Volume 40 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.773
Ranked #31/196 Oncology
(total number of cites)

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APA
Kim, K., Singh, A., Singh, R., DeMartino, A., Brard, L., Vorsa, N., Lange, T., & Moore, R. (2012). Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells. International Journal of Oncology, 40(1), 227-235.
MLA
Kim, Singh, Singh, DeMartino, Brard, Vorsa, Lange, and Richard Moore. "Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells." International Journal of Oncology International Journal of Oncology 40.1 (2012): 227-235.
Chicago
Kim, Singh, Singh, DeMartino, Brard, Vorsa, Lange, and Richard Moore. "Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells." International Journal of Oncology International Journal of Oncology 40 no. 1 (2012): 227-235.