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Volume 2, Issue 3 2017
Journal of Medical Oncology and Therapeutics
Dermatologists & Melanoma 2017
August 31-September 01, 2017
Page 78
&
2
nd
Euro-Global Congress on
August 31-September 01, 2017 London, UK
12
th
Global Dermatologists Congress
Melanoma and Skin Diseases
1, 3-bis (3, 5-dichlorophenyl) urea compound ‘COH-SR4’ inhibits proliferation and activates
apoptosis in melanoma
Kathryn Leake
Oncology Solutions, USA
T
he 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.
kleake@live.unthsc.eduJ Med Oncl Ther 2017, 2:3