<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Liu, L.a</style></author><author><style face="normal" font="default" size="100%">Kritsanida, M.b</style></author><author><style face="normal" font="default" size="100%">Magiatis, P.b</style></author><author><style face="normal" font="default" size="100%">Gaboriaud, N.b</style></author><author><style face="normal" font="default" size="100%">Wang, Y.a</style></author><author><style face="normal" font="default" size="100%">Wu, J.a</style></author><author><style face="normal" font="default" size="100%">Buettner, R.a</style></author><author><style face="normal" font="default" size="100%">Yang, F.a</style></author><author><style face="normal" font="default" size="100%">Nam, S.a</style></author><author><style face="normal" font="default" size="100%">Skaltsounis, L.b</style></author><author><style face="normal" font="default" size="100%">Jove, R.a</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A novel 7-bromoindirubin with potent anticancer activity suppresses survival of human melanoma cells associated with inhibition of STAT3 and Akt signaling</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Biology and Therapy</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">absence of side effects</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">animal cell</style></keyword><keyword><style  face="normal" font="default" size="100%">animal experiment</style></keyword><keyword><style  face="normal" font="default" size="100%">animal model</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">antineoplastic activity</style></keyword><keyword><style  face="normal" font="default" size="100%">Antineoplastic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">article</style></keyword><keyword><style  face="normal" font="default" size="100%">cancer cell destruction</style></keyword><keyword><style  face="normal" font="default" size="100%">cancer chemotherapy</style></keyword><keyword><style  face="normal" font="default" size="100%">cancer inhibition</style></keyword><keyword><style  face="normal" font="default" size="100%">cancer model</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Survival</style></keyword><keyword><style  face="normal" font="default" size="100%">cell viability</style></keyword><keyword><style  face="normal" font="default" size="100%">controlled study</style></keyword><keyword><style  face="normal" font="default" size="100%">drug cytotoxicity</style></keyword><keyword><style  face="normal" font="default" size="100%">drug mechanism</style></keyword><keyword><style  face="normal" font="default" size="100%">drug potency</style></keyword><keyword><style  face="normal" font="default" size="100%">drug safety</style></keyword><keyword><style  face="normal" font="default" size="100%">drug targeting</style></keyword><keyword><style  face="normal" font="default" size="100%">enzyme inhibition</style></keyword><keyword><style  face="normal" font="default" size="100%">enzyme phosphorylation</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">human</style></keyword><keyword><style  face="normal" font="default" size="100%">human cell</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">IC 50</style></keyword><keyword><style  face="normal" font="default" size="100%">in vitro study</style></keyword><keyword><style  face="normal" font="default" size="100%">Inbred BALB C</style></keyword><keyword><style  face="normal" font="default" size="100%">Inbred NOD</style></keyword><keyword><style  face="normal" font="default" size="100%">indirubin</style></keyword><keyword><style  face="normal" font="default" size="100%">Indoles</style></keyword><keyword><style  face="normal" font="default" size="100%">Janus kinase 2</style></keyword><keyword><style  face="normal" font="default" size="100%">Knockout</style></keyword><keyword><style  face="normal" font="default" size="100%">melanoma</style></keyword><keyword><style  face="normal" font="default" size="100%">melanoma cell</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">mitogen activated protein kinase 1</style></keyword><keyword><style  face="normal" font="default" size="100%">mitogen activated protein kinase 3</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitogen-Activated Protein Kinase Kinases</style></keyword><keyword><style  face="normal" font="default" size="100%">mls 2438</style></keyword><keyword><style  face="normal" font="default" size="100%">mouse</style></keyword><keyword><style  face="normal" font="default" size="100%">nonhuman</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphorylation</style></keyword><keyword><style  face="normal" font="default" size="100%">protein kinase B</style></keyword><keyword><style  face="normal" font="default" size="100%">protein tyrosine kinase</style></keyword><keyword><style  face="normal" font="default" size="100%">Proto-Oncogene Proteins c-akt</style></keyword><keyword><style  face="normal" font="default" size="100%">Proto-Oncogene Proteins c-bcl-2</style></keyword><keyword><style  face="normal" font="default" size="100%">SCID</style></keyword><keyword><style  face="normal" font="default" size="100%">signal transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">src-Family Kinases</style></keyword><keyword><style  face="normal" font="default" size="100%">STAT3 protein</style></keyword><keyword><style  face="normal" font="default" size="100%">STAT3 Transcription Factor</style></keyword><keyword><style  face="normal" font="default" size="100%">transcription regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">unclassified drug</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.scopus.com/inward/record.url?eid=2-s2.0-84868363095&amp;partnerID=40&amp;md5=7a1484018e695137b87341f3a823a786</style></url></web-urls></urls><number><style face="normal" font="default" size="100%">13</style></number><volume><style face="normal" font="default" size="100%">13</style></volume><pages><style face="normal" font="default" size="100%">1255-1261</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">STAT3 and Akt signaling have been validated as potential molecular targets for treatment of cancers including melanoma. These small molecule inhibitors of STAT3 or Akt signaling are promising for developing anti-melanoma therapeutic agents. MLS-2438, a novel 7-bromoindirubin, a derivative of the natural product indirubin, was synthesized with a bromo-group at the 7-position on one indole ring and a hydrophilic group at the 3’-position on the other indole ring. We tested the anticancer activity of MLS-2438 and investigated its mechanism of action in human melanoma cell lines. Here, we show that MLS-2438 inhibits viability and induces apoptosis of human melanoma cells associated with inhibition of STAT3 and Akt signaling. Several pro-apoptotic Bcl-2 family proteins are involved in the MLS-2438 mediated apoptosis. MLS-2438 inhibits Src kinase activity in vitro and phosphorylation of JAK2, Src, STAT3 and Akt in cultured cancer cells. In contrast to the decreased phosphorylation levels of JAK2, Src, STAT3 and Akt, phosphorylation levels of the MAP K (Erk1/2) signaling protein were not reduced in cells treated with MLS-2438. These results demonstrate that MLS-2438, a novel natural product derivative, is a Src inhibitor and potentially regulates kinase activity of JAK2 and Akt in cancer cells. Importantly, MLS-2438 suppressed tumor growth with low toxicity in a mouse xenograft model of human melanoma. Our findings support further development of MLS-2438 as a potential small-molecule therapeutic agent that targets both STAT3 and Akt signaling in human melanoma cells. © 2012 Landes Bioscience.</style></abstract><notes><style face="normal" font="default" size="100%">cited By (since 1996)5</style></notes></record></records></xml>