1, 3-Bis (3, 5-dichlorophenyl) urea compound ‘COH-SR4 | 7718
Journal of Clinical & Experimental Dermatology Research

Journal of Clinical & Experimental Dermatology Research
Open Access

ISSN: 2155-9554

+44 1478 350008

1, 3-Bis (3, 5-dichlorophenyl) urea compound ‘COH-SR4’ inhibits proliferation and activates apoptosis in melanoma

Vitiligo and Skincare Physicians Meeting

September 15-16, 2016 Berlin, Germany

Kathryn Leake

Oncology Solutions, USA

Scientific Tracks Abstracts: J Clin Exp Dermatol Res

Abstract :

The current clinical interventions in malignant melanomas are met with poor response to therapy due to dynamic regulation of multiple melanoma signaling pathways following administration of single target agents. In this context of limited response to single target agents, novel candidate molecules capable of effectively inducing tumor inhibition along with targeting multiple critical nodes of melanoma signaling assume translational significance. In this regard, we investigated the anti-cancer effects of a novel dichlorophenyl urea compound called COH-SR4 in melanoma. The SR4 treatment decreased the survival and inhibited the clonogenic potential of melanomas along with inducing apoptosis in the in vitro cultures. SR4 treatments lead to inhibition of GST activity along with causing G2/M phase cell cycle arrest. Oral administration of 4 mg/kg SR4 leads to effective inhibition of tumor burdens in both syngeneic and nude mouse models of melanoma. The SR4 treatment was well tolerated and no overt toxicity was observed. The histopathological examination of resected tumor sections revealed decreased blood vessels, decrease in the levels of angiogenesis marker, CD31 and proliferation marker Ki67, along with an increase in pAMPK levels. Western blot analyses of resected tumor lysates revealed increased PARP cleavage, Bim, pAMPK along with decreased pAkt, vimentin, fibronectin, CDK4 and cyclin B1. Thus, SR4 represents a novel candidate for the further development of mono and combinatorial therapies to effectively target aggressive and therapeutically refractory melanomas.

Biography :

Kathryn Leake has completed her PhD from The University of North Texas Health Science Center and a Postdoctoral Fellowship from Université Laval at Centre de Rechérche de Centre Hospitalier Universital de Quebec. She is the Director of Oncology Solutions, a philanthropic organization that develops drugs for rare cancers. She has provisional patents on treatments for more than 8 malignancies and several publications in reputed journals. She also serves as an Editorial Board Member of Insights in Blood Pressure.