March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Sulindac Protects RPE Cells Against Oxidative Damage but Enhances the Killing of Retinoblastoma Cells Exposed to Oxidative Stress
Author Affiliations & Notes
  • Arunodoy Sur
    Integrative Biology Phd Program, Dept of Biology,
    Florida Atlantic University, Boca Raton, Florida
  • Howard M. Prentice
    Charles E Schimdt College of Medicine,
    Florida Atlantic University, Boca Raton, Florida
  • Herbert Weissbach
    Center For Cellular and Molecualr Biology, Florida Atlantic University, Jupiter, Florida
  • Janet C. Blanks
    Center for Complex Systems & Brain Sci,
    Florida Atlantic University, Boca Raton, Florida
  • Footnotes
    Commercial Relationships  Arunodoy Sur, None; Howard M. Prentice, None; Herbert Weissbach, None; Janet C. Blanks, None
  • Footnotes
    Support  Florida Atlantic University Priority Research Grant (JB)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6884. doi:
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      Arunodoy Sur, Howard M. Prentice, Herbert Weissbach, Janet C. Blanks; Sulindac Protects RPE Cells Against Oxidative Damage but Enhances the Killing of Retinoblastoma Cells Exposed to Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6884.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : The ability of sulindac to enhance killing of the retinoblastoma (RB) cell line, Y79, was tested in combination with reagents that affect mitochondrial function. Recent studies have shown that sulindac can enhance the killing of multiple cancer cell lines, when used in combination with an oxidizing agent. This effect of sulindac was unrelated to the non-steroidal anti-inflammatory activity.

Methods: : The ability of sulindac to kill retinoblastoma cells was determined by treating Y79 cells with sulindac for a period of 48 hours in combination with 3 different chemicals. The three reagents used with sulindac in this study were hydrogen peroxide (H2O2), doxorubicin (DOX) and dichloroacetic acid (DCA). The H2O2 was added for 2 hours after the cells were exposed to sulindac, whereas DOX and DCA were added to the cells along with sulindac for 48 hr. DCA was used at a range of 4uM to 24uM. The DOX concentration ranged from 50nM to 300nM while H2O2 concentration ranged from 250µM to 1.25mM. After treatment with the drugs cellular viability was determined using an assay that utilizes tetrazolium compound (MTS). Conversion of tetrazolium to formazan by cellular dehydrogenase in metabolically active cells was detected by colorimetric analysis

Results: : The results show that exposing cultured Y79 cells to sulindac, combined with anti-cancer agents that affect mitochondrial function, such as DCA or DOX, causes increased death of cancer cells. The combination of the two drugs resulted in death of about 30% of Y79 cells under conditions where sulindac or anti-cancer agents that affect mitochondrial function alone caused no loss of cell viability.

Conclusions: : We reported previously that sulindac protected RPE cells from increased oxidative stress induced by oxidizing agents. In contrast, the killing of cancer cells by sulindac and oxidizing agents involve mitochondrial dysfunction, reactive oxygen species production and apoptosis. Evidence is presented that sulindac enhances the killing of RB cells exposed to agents that affect mitochondrial function. Future experiments will study the role of mitochondria and ROS and elucidate the signaling mechanisms involved in this process. This combination therapy using sulindac represents a novel therapeutic approach to treat RB.

Keywords: retinoblastoma • retinal pigment epithelium • oxidation/oxidative or free radical damage 

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