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A Novel Resveratrol Analog : Its Cell Cycle Inhibitory, Pro-Apoptotic and Anti-Inflammatory Activities on Human Tumor Cells

Lin, Boren
http://rave.ohiolink.edu/etdc/view?acc_num=kent1144769442

Abstract Details

2006, PHD, Kent State University, School of Biomedical Sciences.
Resveratrol has been considered a chemopreventive and therapeutic candidate against carcinogenesis because of its potential to modulate multiple molecular pathways associated with the development and progression of cancer. Novel resveratrol analogs were developed, tested and compared with resveratrol. Anti-proliferatory activity of resveratrol, KSA and KST compounds were demonstrated. Amount them, KST201 was the most selective compound against cancer cell growth according to its cytotoxicity selective index value. Resveratrol blocked cell cycle of hormone-independent prostate cancer DU145 cells in the G0/G1 phase, and a subG0/G1 peak was present. KST201 caused DU145 cell cycle arrest in the G0/G1 phase. In ovarian cancer MDAH cells and bladder cancer T24 cells, KST201 blocked cell cycle in the S phase. KST201 induced apoptotic subG0/G1 cell population in DU145, MDAH and T24 cells. Resveratrol and KST201 produced cytoplasmic DNA fragments, induced caspase-3 activity and caused morphological changes in DU145 cells. These findings confirmed the pro-apoptotic activity of these two compounds. Activation of NF-kappa B was inhibited in resveratrol- and KST201-treated DU145. Both resveratrol and KST201 attenuated cyclooxygenase enzymatic activity but were shown more specific to cyclooxygenase-1. Antioxidant activity of resveratrol was shown in solutions containing free radicals; however, KST201 was less effective on free radical scavenging. Resveratrol inhibited 2'7'-dichlorofluorescin oxidation mediated by hydrogen peroxide, whereas KST201 increased it. Depletion of hydrogen peroxide inhibited anti-proliferatory activity of KST201 but not resveratrol. Contrary to resveratrol, KST201 behaved as a pro-oxidant rather than an antioxidant suggesting a different role it played in the biological system examined in this study. Compared to resveratrol-treated DU145, a broader spectrum of genes were regulated in KST201-treated cells. These genes encode proteins involved in various signaling pathways controlling cancer formation. 57% of resveratrol-regulated genes were induced or suppressed by KST201 indicating the overlap of signaling molecules targeted by these two compounds.
Chun-Che Tsai (Advisor)
KST201; RESVERATROL; DU145; CELL; Resveratrol and KST201; KST201-treated; NF-kappa

Recommended Citations

Citations

  • Lin, B. (2006). A Novel Resveratrol Analog : Its Cell Cycle Inhibitory, Pro-Apoptotic and Anti-Inflammatory Activities on Human Tumor Cells [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1144769442

    APA Style (7th edition)

  • Lin, Boren. A Novel Resveratrol Analog : Its Cell Cycle Inhibitory, Pro-Apoptotic and Anti-Inflammatory Activities on Human Tumor Cells. 2006. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1144769442.

    MLA Style (8th edition)

  • Lin, Boren. "A Novel Resveratrol Analog : Its Cell Cycle Inhibitory, Pro-Apoptotic and Anti-Inflammatory Activities on Human Tumor Cells." Doctoral dissertation, Kent State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=kent1144769442

    Chicago Manual of Style (17th edition)

kent1144769442
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© 2006, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.