Proopiomelanocortin gene delivery induces apoptosis in melanoma through NADPH oxidase 4-mediated ROS generation
Guei-Sheung Liu, Jian-Ching Wu, Han-En Tsai, Gregory J Dusting, Elsa C Chan, Chieh-Shan Wu, Ming-Hong Tai
FREE RADICAL BIOLOGY AND MEDICINE | ELSEVIER SCIENCE INC | Published : 2014
Hypoxia in the tumor microenvironment triggers differential signaling pathways for tumor survival. In this study, we characterize the involvement of hypoxia and reactive oxygen species (ROS) generation in the antineoplastic mechanism of proopiomelanocortin (POMC) gene delivery in a mouse B16-F10 melanoma model in vivo and in vitro. Histological analysis revealed increased TUNEL-positive cells and enhanced hypoxic activities in melanoma treated with adenovirus encoding POMC (Ad-POMC) but not control vector. Because the apoptotic cells were detected mainly in regions distant from blood vessels, it was hypothesized that POMC therapy might render melanoma cells vulnerable to hypoxic insult. Usin..View full abstract
Awarded by National Science Council, Taiwan
Awarded by Kaohsiung Veterans General Hospital, Taiwan
This work was supported by grants from the National Science Council, Taiwan (NSC 100-2325-B-110-002-MY3), Kaohsiung Veterans General Hospital, Taiwan (MF-DLC 98029S4 and MF-DLC 99053S4), National Sun Yat-Sen University, and the Ophthalmic Research Institute of Australia. G.S.L. receives the Early Career Researcher Fellowship (from University of Melbourne). G.J.D. receives a Principal Research Fellowship from NHMRC. G.S.L. and E.C.C. are supported by The Ansell Ophthalmology Foundation. J.C.W. is supported by the Graduate Program in Marine Biotechnology. The Centre for Eye Research Australia receives operational infrastructure support from the Victorian government.