Role of antioxidants and intracellular free radicals in retinamide-induced cell death

Carcinogenesis
D DeliaM A Pierotti

Abstract

The cancer chemopreventive synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR) possesses antiproliferative and apoptotic activity at pharmacological doses. In this study we show that addition of antioxidants to HL-60 cells cultured in the presence of 3 microM HPR, markedly suppresses the apoptopic effect of the retinoid and significantly prolongs cell survival (48-96 h). We also show, by the use of the oxidation-sensitive probe 2',7'-dichlorofluorescin diacetate (DCF-DA) and in combination with flow cytometric and spectrofluorimetric analysis, that treatment of cells with 3 microM HPR results in an immediate and sustained production of intracellular free radicals, most likely hydroperoxides. Interestingly, the formation of these HPR-induced free radicals is effectively blocked by the water soluble antioxidants L-ascorbic acid and N-acetyl-L-cysteine. Neither 3-15 microM N-(4-methoxyphenyl) retinamide (MPR), the structurally similar but biologically inert analog of HPR, nor 3 microM doses of the retinoids all-trans retinoic acid, 9-cis-retinoic acid, TTNPB and SR11237 induce intracellular free radicals, thus indicating that the specificity of this phenomenon is restricted to HPR. Altogether, we provide the first direct eviden...Continue Reading

Citations

Nov 28, 2000·International Journal of Cancer. Journal International Du Cancer·P E LovatC P Redfern
Sep 1, 2005·Apoptosis : an International Journal on Programmed Cell Death·N Hail
Jul 20, 2006·Apoptosis : an International Journal on Programmed Cell Death·N HailR Lotan
May 27, 2005·Journal of Biomedical Science·Li-Jyun YangYat-Pang Chau
Dec 21, 2000·Current Oncology Reports·R Torrisi, A Decensi
Dec 21, 2000·Current Oncology Reports·C P Reynolds
Mar 12, 2004·Cancer Letters·C Patrick ReynoldsRichard N Kolesnick
Jul 26, 2003·Cancer Letters·C Patrick ReynoldsBarry J Maurer
Nov 30, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·F Formelli, L Cleris
Jan 12, 2001·Journal of Photochemistry and Photobiology. B, Biology·S E TobiT J McMillan
Sep 19, 2002·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Maria A OrtizF Javier Piedrafita
Oct 30, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A GadducciR Tana
Jul 7, 1999·Journal of the National Cancer Institute·J C Reed
May 6, 2004·Journal of the National Cancer Institute·Shi-Yong SunReuben Lotan
Sep 2, 2004·Journal of the National Cancer Institute·Ethan Dmitrovsky
May 20, 1999·Annual Review of Pharmacology and Toxicology·M D Collins, G E Mao
Sep 17, 2010·Journal of Signal Transduction·Vivian R RuvoloPeter P Ruvolo
Apr 14, 2012·Journal of Biomedicine & Biotechnology·Massimiliano CazzanigaAliana Guerrieri-Gonzaga
Dec 25, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shoichiro ShishidoMichio Sata
Aug 27, 2002·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·B A Stoll
Apr 13, 2007·Expert Review of Anticancer Therapy·Bernardo BonanniUmberto Veronesi
Oct 31, 2003·Expert Opinion on Investigational Drugs·Winfred MaloneHoward Higley
Nov 2, 2011·The Breast : Official Journal of the European Society of Mastology·Matteo LazzeroniAndrea DeCensi
Feb 8, 2005·Clinical Lung Cancer·Konstantin H DragnevEthan Dmitrovsky
May 6, 2008·Free Radical Biology & Medicine·Numsen HailJulian E Spallholz
Jan 22, 2004·International Journal of Cancer. Journal International Du Cancer·Hye-Sook HanSoo-Jong Um
May 4, 2006·International Journal of Cancer. Journal International Du Cancer·Stefano CaramutaDomenico Delia
May 4, 2005·Biochemical and Biophysical Research Communications·Marco CorazzariMauro Piacentini
Oct 6, 2005·Bioorganic & Medicinal Chemistry·Noriko TakahashiToshihiro Ohba
Jan 5, 2002·Hematology/oncology Clinics of North America·C P Reynolds, R S Lemons
May 27, 2005·Free Radical Biology & Medicine·Wai-Lung Lai, Nai-Sum Wong
Sep 30, 2000·Experimental Cell Research·P E LovatC P Redfern
Aug 17, 1999·Cancer Treatment Reviews·E Ulukaya, E J Wood

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