Open Access

The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells

  • Authors:
    • Yifei Wang
    • Alex Han
    • Eva Chen
    • Rakesh K. Singh
    • Clinton O. Chichester
    • Richard G. Moore
    • Ajay P. Singh
    • Nicholi Vorsa
  • View Affiliations

  • Published online on: March 17, 2015     https://doi.org/10.3892/ijo.2015.2931
  • Pages: 1924-1934
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their antioxidant properties, have been shown to possess potential in vitro activity against several cancers. However, the difficulty of isolating cranberry compounds has largely limited anticancer research to crude fractions without well-defined compound composition. In this study, individual cranberry flavonoids were isolated to the highest purity achieved so far using gravity and high performance column chromatography and LC-MS characterization. MTS assay indicated differential cell viability reduction of SKOV-3 and OVCAR-8 ovarian cancer cells treated with individual cranberry flavonoids. Treatment with quercetin aglycone and PAC DP-9, which exhibited the strongest activity, induced apoptosis, led to caspase-3 activation and PARP deactivation, and increased sensitivity to cisplatin. Furthermore, immunofluorescence microscopy and western blot study revealed reduced expression and activation of epidermal growth factor receptor (EGFR) in PAC DP-9 treated SKOV-3 cells. In addition, quercetin aglycone and PAC DP-9 deactivated MAPK-ERK pathway, induced downregulation of cyclin D1, DNA-PK, phospho-histone H3 and upregulation of p21, and arrested cell cycle progression. Overall, this study demonstrates promising in vitro cytotoxic and anti-proliferative properties of two newly characterized cranberry flavonoids, quercetin aglycone and PAC DP-9, against ovarian cancer cells.
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May-2015
Volume 46 Issue 5

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

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Spandidos Publications style
Wang Y, Han A, Chen E, Singh RK, Chichester CO, Moore RG, Singh AP and Vorsa N: The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells. Int J Oncol 46: 1924-1934, 2015
APA
Wang, Y., Han, A., Chen, E., Singh, R.K., Chichester, C.O., Moore, R.G. ... Vorsa, N. (2015). The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells. International Journal of Oncology, 46, 1924-1934. https://doi.org/10.3892/ijo.2015.2931
MLA
Wang, Y., Han, A., Chen, E., Singh, R. K., Chichester, C. O., Moore, R. G., Singh, A. P., Vorsa, N."The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells". International Journal of Oncology 46.5 (2015): 1924-1934.
Chicago
Wang, Y., Han, A., Chen, E., Singh, R. K., Chichester, C. O., Moore, R. G., Singh, A. P., Vorsa, N."The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells". International Journal of Oncology 46, no. 5 (2015): 1924-1934. https://doi.org/10.3892/ijo.2015.2931