Targeting multiple key signaling pathways in melanoma using leelamine.

ABSTRACT: Melanoma is a highly drug-resistant cancer with resistance developing to agents targeting single proteins. To circumvent this problem, a new class of agent inhibiting multiple key pathways important in this disease is being developed to reduce the likelihood of developing resistant disease. The phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and STAT3 pathways are constitutively activated in 50% to 70% of melanomas, promoting disease development. To identify a drug simultaneously targeting the PI3K, MAPK, and STAT3 cascades, a natural product library was screened to identify leelamine as a potential inhibitor. Leelamine was 4.5-fold more effective at inhibiting cultured melanoma cell survival than normal cells, with average IC(50) values of 2 and 9.3 μmol/L, resp

SUBMITTER: Gowda R 

PROVIDER: S-EPMC4377161 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature