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

Kyu Kwang Kim, Ajay P. Singh, Rakesh K. Singh, Angelica DeMartino, Laurent Brard, Nicholi Vorsa, Thilo S. Lange, Richard G. Moore

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)227-235
Number of pages9
JournalInternational journal of oncology
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Vaccinium macrocarpon
Proanthocyanidins
Ovarian Neoplasms
Reactive Oxygen Species
Endothelial Cells
Therapeutics
Vascular Endothelial Growth Factor Receptor
proanthocyanidin
G2 Phase
Human Umbilical Vein Endothelial Cells
Cell Division
Antineoplastic Agents
Glutathione
Cell Survival
Cell Cycle
Antioxidants
Phosphorylation
Apoptosis
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Angiogenesis
  • Cranberry
  • Ovarian cancer
  • Proanthocyanidin
  • Reactive oxygen species

Cite this

Kim, Kyu Kwang ; Singh, Ajay P. ; Singh, Rakesh K. ; DeMartino, Angelica ; Brard, Laurent ; Vorsa, Nicholi ; Lange, Thilo S. ; Moore, Richard G. / Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells. In: International journal of oncology. 2012 ; Vol. 40, No. 1. pp. 227-235.
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Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells. / Kim, Kyu Kwang; Singh, Ajay P.; Singh, Rakesh K.; DeMartino, Angelica; Brard, Laurent; Vorsa, Nicholi; Lange, Thilo S.; Moore, Richard G.

In: International journal of oncology, Vol. 40, No. 1, 01.01.2012, p. 227-235.

Research output: Contribution to journalArticle

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