The novel synthetic oleanane triterpenoid CDDO (2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid) induces apoptosis in Mycosis fungoides/Sézary syndrome cells

The Journal of Investigative Dermatology
Chunlei ZhangMadeleine Duvic

Abstract

The novel synthetic oleanane triterpenoid CDDO (2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid) can serve as a ligand for the peroxisome proliferator activator receptor-gamma (PPAR-gamma) and has been shown to inhibit cell proliferation, and to induce differentiation and apoptosis in tumor cell lines. Bexarotene is an RXR-selective retinoid that can induce apoptosis of mycosis fungoides (MF) and Sézary syndrome (SS) cells. Since the PPAR-gamma and RXR receptors can form heterodimers, we studied the effects of CDDO and its synergism with bexarotene on apoptosis in MF/SS cell lines (MJ, Hut78, and HH) and freshly isolated peripheral blood lymphocytes (PBL) from SS patients with circulating atypical T cells (CD4+CD26-). CDDO treatment at 1-5 microM for 48 h caused a concentration-dependent apoptosis in three MF/SS cell lines and patients' PBL compared to vehicle controls. Bexarotene augmented CDDO-induced apoptosis in these cells. PPAR-gamma was expressed but decreased by 47% in MJ, 42% in Hut78, and 77% in HH cells following CDDO treatment. The anti-apoptotic protein bcl-xL, but not bcl-2, was decreased by 69% in MJ, 31% in Hut78, and 59% in HH cells and caspase-3 was activated following CDDO treatment. Interestingly, the PPAR-ga...Continue Reading

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Citations

May 23, 2008·The Journal of Investigative Dermatology·Chunlei ZhangMadeleine Duvic
Oct 4, 2006·Dermatologic Therapy·Chunlei Zhang, Madeleine Duvic
Nov 25, 2011·Journal of the European Academy of Dermatology and Venereology : JEADV·R YoussefO G Shaker
Apr 26, 2006·Expert Opinion on Pharmacotherapy·Christiane QuerfeldJoan Guitart
Nov 9, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Li Xiao RuiTang Ze Yao
Dec 23, 2006·Journal of the American Academy of Dermatology·Jacob A SepmeyerJohn A Zic
Dec 24, 2013·European Journal of Medicinal Chemistry·Bianka SiewertRené Csuk
Jun 3, 2006·Natural Product Reports·Petr DzubakJan Sarek
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Oct 12, 2017·Frontiers in Molecular Neuroscience·Namrata ChaudhariPalaniyandi Ravanan
Jun 21, 2014·The British Journal of Dermatology·R van Doorn
Sep 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seung-Hee JoY Lynn Wang
Jul 2, 2019·Science & Justice : Journal of the Forensic Science Society·Paula Núñez MartínezSara C Zapico

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