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Roles of survivin isoforms in the chemopreventive actions of NSAIDS on colon cancer cells

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Abstract

NSAIDs downregulate survivin (an apoptosis inhibitor), increase apoptosis and reduce growth of colon polyps and cancers. Recently, anti- and pro-apoptosis isoforms of survivin were identified. The roles of these isoforms in NSAID-induced colon cancer cell death have not been examined, and is the focus of this study. The anti-apoptosis isoforms, wild-type (WT) survivin and survivin-ΔEx3, and the pro-apoptosis isoform, survivin-2b, were present in HT-29 and RKO cells. Indomethacin treatment significantly decreased WT survivin and survivin-ΔEx3 (30.5±10.4% and 20.3±6.7%, respectively) but not survivin-2b mRNA in RKO cells. In HT-29 cells, all three isoform mRNAs were slightly decreased by indomethacin treatment. Consistently, indomethacin treatment dramatically reduced WT survivin protein in RKO but not HT-29 cells. Indomethacin treatment increased apoptosis and general cell death more significantly in RKO cells (75.7±1.1% cell death at 48 h) than in HT-29 cells (25.4±3.7% cell death at 48 h). Anti-sense suppression of survivin-2b mRNA increased resistance of both RKO and HT-29 cells to indomethacin. These data support a role for survivin isoforms in colon cancer cell apoptosis, and thus in prevention of colon cancer growth by NSAIDs.

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Acknowledgments

This work is supported by the VA Merit Review Entry Program Award to Dr. S.-K. Chiou.

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Authors and Affiliations

  1. Division of Gastroenterology, VA Medical Center, 5901 E. Seventh Street-111, Long Beach, CA, 90822, USA

    Sarathy Mandayam, Richard Huang, Andrzej S. Tarnawski & Shiun-Kwei Chiou

  2. University of California Irvine, Irvine, CA, USA

    Sarathy Mandayam, Richard Huang, Andrzej S. Tarnawski & Shiun-Kwei Chiou

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  1. Sarathy Mandayam
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  2. Richard Huang
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  3. Andrzej S. Tarnawski
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  4. Shiun-Kwei Chiou
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Correspondence to Shiun-Kwei Chiou.

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Mandayam, S., Huang, R., Tarnawski, A.S. et al. Roles of survivin isoforms in the chemopreventive actions of NSAIDS on colon cancer cells. Apoptosis 12, 1109–1116 (2007). https://doi.org/10.1007/s10495-006-0011-2

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  • DOI: https://doi.org/10.1007/s10495-006-0011-2

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