Radiosensitizing and anti-proliferative effects of resveratrol in two human cervical tumor cell lines

Imran Zoberi, C. Matthew Bradbury, Heather A. Curry, Kheem S. Bisht, Prabhat C. Goswami, Joseph L. Roti Roti, David Gius

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Resveratrol is a polyphenol isolated from the skins of grapes that has been shown to significantly alter the cellular physiology of tumor cells, as well as block the process of initiation and progression. At least one mechanism for the intracellular actions of resveratrol involves the suppression of prostaglandin (PG) biosynthesis. The involvement of PGs and other eicosanoids in the development of human cancer is well established. PGs are synthesized from arachidonic acid via the cyclooxygenase pathway and have multiple physiological and pathological functions. In addition, evidence has arisen suggesting that PGs may be implicated in the cytotoxic and/or cytoprotective response of tumor cells to ionizing radiation (IR). As such, we hypothesized that tumor cells may exhibit changes in the cellular response to IR following exposure to resveratrol, a naturally occuring compound that inhibits cyclooxygenase-1 (COX-1) activity. Thus, clonogenic cell survival assays were performed using irradiated HeLa and SiHa cells pretreated with resveratrol prior to IR exposure, and resulted in enhanced tumor cell killing by IR in a dose-dependent manner. Further analysis of COX-1 inhibition indicated that resveratrol pretreatment: (1), inhibited cell division as assayed by growth curves; and (2), induced an early S phase cell cycle checkpoint arrest, as demonstrated by fluorescence-activated cell sorting, as well as bromodeoxyuridine pulse-chase analysis. These results suggest that resveratrol alters both cell cycle progression and the cytotoxic response to IR in two cervical tumor cell lines.

Original languageEnglish
Pages (from-to)165-173
Number of pages9
JournalCancer Letters
Volume175
Issue number2
DOIs
StatePublished - Jan 25 2002

Keywords

  • Cell cycle
  • Cyclooxygenase
  • Cyclooxygenase-1
  • Cytotoxicity
  • Ionizing radiation

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    Zoberi, I., Bradbury, C. M., Curry, H. A., Bisht, K. S., Goswami, P. C., Roti Roti, J. L., & Gius, D. (2002). Radiosensitizing and anti-proliferative effects of resveratrol in two human cervical tumor cell lines. Cancer Letters, 175(2), 165-173. https://doi.org/10.1016/S0304-3835(01)00719-4