Showing papers by "Komal Raina published in 2011"

Silibinin Prevents Lung Tumorigenesis in Wild-Type but not in iNOS−/− Mice: Potential of Real-Time Micro-CT in Lung Cancer Chemoprevention Studies

Abstract: Purpose: Sustained nitric oxide (NO) generation positively correlates with lung cancer development and progression. Herein, we genetically confirmed this role of iNOS and evaluated the chemopreventive efficacy of silibinin in carcinogen-treated B6/129 wild-type (WT) and iNOS −/− mice. Experimental Design: Male B6/129-Nos2 tm1Lau (iNOS −/− ) and B6/129PF2 WT mice were injected i.p. with 1 mg/g body weight urethane once weekly for 7 consecutive weeks, followed by silibinin gavage (742 mg/kg body weight) for 5 d/wk for 18 weeks. Results: Quantification of micro-CT data in real-time showed that silibinin significantly decreases urethane-induced tumor number and size in WT mice, consistent with measurements made ex vivo at study termination. Genetic ablation of iNOS decreased urethane-induced tumor multiplicity by 87% ( P P −/− mice. Tumors from WT mice expressed more iNOS ( P P P Conclusions: The lack of effect of silibinin in iNOS −/− mice suggests that silibinin exerts most of its chemopreventive and angiopreventive effects through its inhibition of iNOS expression in lung tumors. Our results support iNOS as a potential target for controlling lung cancer, and demonstrate the value of real-time noninvasive micro-CT imaging modality for evaluating the efficacy of lung cancer chemopreventive agents. Clin Cancer Res; 17(4); 1–9. ©2010 AACR .