Aerosolized Bexarotene Inhibits Lung Tumorigenesis without Increasing Plasma Triglyceride and Cholesterol Levels in Mice

Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Cancer Prevention Research (Impact Factor: 4.44). 02/2011; 4(2):270-6. DOI: 10.1158/1940-6207.CAPR-10-0246
Source: PubMed


Prior studies have shown the retinoid X receptor (RXR) agonist bexarotene has preventive efficacy in rodent models of mammary and lung tumorigenesis albeit causing hypertriglyceridemia and hypercholesterolemia. We reasoned that bexarotene delivered by inhalation may provide sufficient dose directly to the respiratory tract to achieve efficacy while avoiding these side effects. In this study, the chemopreventive activity of aerosolized bexarotene was investigated in the benzo(a)pyrene [B(a)P]-induced mouse lung tumor model as assessed by tumor multiplicity and tumor load. Aerosolized bexarotene significantly decreased tumor multiplicity and tumor load by 43% and 74%, respectively. Our data showed that bexarotene can both inhibit proliferation and promote apoptosis in vivo. Our data also show that aerosolized bexarotene did not increase plasma total cholesterol and triglyceride level compared with diet group. These results indicate that aerosolization may be a safe and effective route of administering bexarotene for chemoprevention of lung cancer.

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    • "There has been significant interest in this class of compounds in cancer because an RXR agonist [Targretin (TRG)] is approved clinically for the treatment of cutaneous T-cell lymphoma (Lansigan and Foss 2010) and has demonstrated clinical efficacy in non–small-cell lung cancer (Dragnev et al., 2011; Kim et al., 2011). In addition, this class of compounds has shown efficacy in a variety of mammary and lung cancer models in rodents (Pereira et al., 2006; Wang et al., 2006b, 2009; Liby, et al., 2007; Zhang et al., 2011), and more recently in humans (Dragnev et al., 2011; Kim et al., 2011). However, the elevation of triglycerides levels by 9-cis-RA, TRG, and various retinoids has been known for many years and is a major concern in the use of these agents, particularly in a cancer-prevention setting (Grubbs et al., 2006; Kolesar et al., 2010). "
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    Molecular pharmacology 01/2013; 83(3). DOI:10.1124/mol.112.082404 · 4.13 Impact Factor
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    Advances in Cancer Therapy, 11/2011; , ISBN: 978-953-307-703-1
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