Synergistic action of dietary phyto-antioxidants on survival and proliferation of ovarian cancer cells

Madhwa H G Raj, Zakaria Y. Abd Elmageed, Jing Zhou, RL L. Gaur, Lan Nguyen, Ghazala A. Azam, Patricia Braley, Prakash N. Rao, Ismail M. Fathi, Allal Ouhtit

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objectives: A number of herbal dietary antioxidant supplements containing Indole-3 Carbinol (I3C) and Resveratrol (RE) have been established as anti-proliferative agents in cancer. These compounds have both similar as well as unique molecular targeting profiles. The purpose of this study is to analyze their mechanism of action when used individually and in combination in ovarian cancer. Methods: SK-OV-3 ovarian cancer cells were treated with various doses of I3C, RE or I3C+RE. AlamarBlue dye assay was used to examine cell growth and proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to determine the expression of the genes associated with cell cycle and apoptosis. CA-125, a functional marker of ovarian cancer, and nitric oxide, were analyzed by ELISA. Results: I3C or RE inhibited cell proliferation, and caused cell contraction and apoptosis. Analysis of apoptosis-associated genes revealed an inhibition of Retinoblastoma protein (Rb) and Survivin (SVV) gene expression. This was accompanied by elevation of p21, a tumor suppressor. Cell cycle was inhibited at both G1 and G2/M by individual treatments, and accentuated by a combination. AlamarBlue assay revealed a clear synergistic action of I3C+RE. CA125 was inhibited by either I3C or RE treatments. In contrast, basal nitric oxide production was inhibited by I3C and I3C+RE but not RE alone. Conclusions: This is the first evidence demonstrating the effects of I3C on ovarian cancer cells and its synergism with RE. Based on this model, our data indicate that combinations of compounds with different targeting properties will be more effective in chemoprevention and/or chemotherapy of ovarian and possibly other cancers.

Original languageEnglish
Pages (from-to)432-438
Number of pages7
JournalGynecologic Oncology
Volume110
Issue number3
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Ovarian Neoplasms
Antioxidants
Apoptosis
Cell Cycle
Nitric Oxide
Cell Proliferation
Retinoblastoma Genes
Gene Expression
indole-3-carbinol
resveratrol
Neoplasms
Retinoblastoma Protein
Chemoprevention
Dietary Supplements
Flow Cytometry
Coloring Agents
Western Blotting
Enzyme-Linked Immunosorbent Assay
Drug Therapy
Therapeutics

Keywords

  • Apoptosis
  • Cell cycle
  • Indol-3-Carbinol
  • Ovarian Cancer
  • Resveratrol
  • Survivin (SVV)

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

Raj, M. H. G., Abd Elmageed, Z. Y., Zhou, J., Gaur, RL. L., Nguyen, L., Azam, G. A., ... Ouhtit, A. (2008). Synergistic action of dietary phyto-antioxidants on survival and proliferation of ovarian cancer cells. Gynecologic Oncology, 110(3), 432-438. https://doi.org/10.1016/j.ygyno.2008.05.001

Synergistic action of dietary phyto-antioxidants on survival and proliferation of ovarian cancer cells. / Raj, Madhwa H G; Abd Elmageed, Zakaria Y.; Zhou, Jing; Gaur, RL L.; Nguyen, Lan; Azam, Ghazala A.; Braley, Patricia; Rao, Prakash N.; Fathi, Ismail M.; Ouhtit, Allal.

In: Gynecologic Oncology, Vol. 110, No. 3, 09.2008, p. 432-438.

Research output: Contribution to journalArticle

Raj, MHG, Abd Elmageed, ZY, Zhou, J, Gaur, RLL, Nguyen, L, Azam, GA, Braley, P, Rao, PN, Fathi, IM & Ouhtit, A 2008, 'Synergistic action of dietary phyto-antioxidants on survival and proliferation of ovarian cancer cells', Gynecologic Oncology, vol. 110, no. 3, pp. 432-438. https://doi.org/10.1016/j.ygyno.2008.05.001
Raj, Madhwa H G ; Abd Elmageed, Zakaria Y. ; Zhou, Jing ; Gaur, RL L. ; Nguyen, Lan ; Azam, Ghazala A. ; Braley, Patricia ; Rao, Prakash N. ; Fathi, Ismail M. ; Ouhtit, Allal. / Synergistic action of dietary phyto-antioxidants on survival and proliferation of ovarian cancer cells. In: Gynecologic Oncology. 2008 ; Vol. 110, No. 3. pp. 432-438.
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AU - Nguyen, Lan

AU - Azam, Ghazala A.

AU - Braley, Patricia

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