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HUMAN NEUROBLASTOMA CELLS RAPIDLY ENTER CELL CYCLE ARREST AND APOPTOSIS FOLLOWING EXPOSURE TO C-28 DERIVATIVES OF THE SYNTHETIC TRITERPENOID CDDO

Alabran, Jennifer L.
http://rave.ohiolink.edu/etdc/view?acc_num=case1253290381

Abstract Details

2010, Master of Sciences, Case Western Reserve University, Pathology.
Synthetic triterpenoids, such as 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid (CDDO) and its derivatives, belong to an extremely potent class of new anti-cancer therapeutic agents characterized by high anti-tumor potency and low toxicity to normal tissue. This work is the first to investigate the effects of C-28 derivatives of CDDO in several pediatric solid tumor cell lines in vitro and in a mouse xenograft model of human neuroblastoma. Using C-28 CDDO analogs we determined an IC50 in the range of 5 – 630 nM depending on the method used. We show partial G2/M arrest, conformational activation and mitochondrial translocation of Bax protein, as well as activation of caspases -3 and -8 following treatment with CDDO-Me. Tumor xenograft experiments in mice demonstrated a significant delay in tumor growth in mice fed a diet containing CDDO-Me. Overall, CDDO analogs appear to be promising for development as novel therapeutic agents for these high-risk pediatric solid tumors.
John Letterio, MD (Advisor)
James Anderson, MD PhD (Committee Chair)
Nicholas Ziats, PhD (Committee Member)
55 p.
CDDO; NEUROBLASTOMA; TRITERPENOID; CELLS; NEUROBLASTOMA CELLS; tumor; Cancers

Recommended Citations

Citations

  • Alabran, J. L. (2010). HUMAN NEUROBLASTOMA CELLS RAPIDLY ENTER CELL CYCLE ARREST AND APOPTOSIS FOLLOWING EXPOSURE TO C-28 DERIVATIVES OF THE SYNTHETIC TRITERPENOID CDDO [Master's thesis, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1253290381

    APA Style (7th edition)

  • Alabran, Jennifer. HUMAN NEUROBLASTOMA CELLS RAPIDLY ENTER CELL CYCLE ARREST AND APOPTOSIS FOLLOWING EXPOSURE TO C-28 DERIVATIVES OF THE SYNTHETIC TRITERPENOID CDDO. 2010. Case Western Reserve University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1253290381.

    MLA Style (8th edition)

  • Alabran, Jennifer. "HUMAN NEUROBLASTOMA CELLS RAPIDLY ENTER CELL CYCLE ARREST AND APOPTOSIS FOLLOWING EXPOSURE TO C-28 DERIVATIVES OF THE SYNTHETIC TRITERPENOID CDDO." Master's thesis, Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1253290381

    Chicago Manual of Style (17th edition)

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© 2009, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.