You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2012307 BISEBROMOAMIDE, AS A NOVEL MOLECULAR TARGET DRUG INHIBITING PHOSPHORYLATION OF BOTH EXTRACELLULAR SIGNAL-REGULATED KINASE AND AKT IN RENAL CELL CARCINOMA Kenjiro Suzuki, Ryuichi Mizuno, Kiyotake Suenaga, Takeo Kosaka, Nobuyuki Tanaka, Kazunobu Shinoda, Hidaka Kono, Eiji Kikuchi, Hirohiko Nagata, Hiroshi Asanuma, Akira Miyajima, Ken Nakagawa, and Mototsugu Oya Kenjiro SuzukiKenjiro Suzuki Tokyo, Japan More articles by this author , Ryuichi MizunoRyuichi Mizuno Tokyo, Japan More articles by this author , Kiyotake SuenagaKiyotake Suenaga Yokohama, Japan More articles by this author , Takeo KosakaTakeo Kosaka Tokyo, Japan More articles by this author , Nobuyuki TanakaNobuyuki Tanaka Tokyo, Japan More articles by this author , Kazunobu ShinodaKazunobu Shinoda Tokyo, Japan More articles by this author , Hidaka KonoHidaka Kono Tokyo, Japan More articles by this author , Eiji KikuchiEiji Kikuchi Tokyo, Japan More articles by this author , Hirohiko NagataHirohiko Nagata Tokyo, Japan More articles by this author , Hiroshi AsanumaHiroshi Asanuma Tokyo, Japan More articles by this author , Akira MiyajimaAkira Miyajima Tokyo, Japan More articles by this author , Ken NakagawaKen Nakagawa Tokyo, Japan More articles by this author , and Mototsugu OyaMototsugu Oya Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.366AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Mitogen-activated protein kinase (MAPK) pathway typified by MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway and the Akt/mammalian target of rapamycin (mTOR) pathway are representative cellular survival and proliferation signaling pathways. Bisebromoamide (BBA) has been isolated from the marine cyanobacterium Lyngbya species at our laboratory in 2009, which inhibits the phosphorylation of ERK specifically in normal rat kidney (NRK) cells. If the same effect can be shown in human renal cell carcinoma (RCC), BBA is expected to become a novel molecular target drug. The aim of this study is to elucidate the effect of BBA for human RCC. METHODS 2 human RCC cell lines, 769-P and 786-O were used. The effect of BBA on cell proliferation was analyzed by WST-1 assay. The expression of phosphorylated ERK (p-ERK), total ERK, phosphorylated Akt (p-Akt) and total Akt was analyzed by Western blotting treated with 1μM of BBA for 3, 6, 12, 24 hours. Apoptosis was determined by flow cytometric Terminal deoxynucleotidyl Transferase (TdT)-mediated 2'-Deoxyuridine 5'-Triphosphate (dUTP) nick end labeling (TUNEL) analysis. RESULTS BBA suppressed proliferation in 769-P with 50% inhibitory concentration (IC50) values of 1.63μM. Also in 786-O, the similar result was obtained with IC50 values of 2.11μM (Figure 1). BBA inhibited the phosphorylation of ERK and Akt in 2 RCC cell lines by treatment with 1μM of BBA time-dependently without affecting the activity of total ERK and Akt (Figure 2). Apoptosis was induced in both cell lines treated with 1μM of BBA for 72 hours. The percentage of apoptotic cells was 30.0% in 769-P, and 44.2% in 786-O, respectively. CONCLUSIONS BBA suppresses proliferation inhibiting phosphorylation of both ERK and Akt resulted in inducing apoptosis in human RCC. BBA is expected to be a promising agent targeting RCC. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e124-e125 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kenjiro Suzuki Tokyo, Japan More articles by this author Ryuichi Mizuno Tokyo, Japan More articles by this author Kiyotake Suenaga Yokohama, Japan More articles by this author Takeo Kosaka Tokyo, Japan More articles by this author Nobuyuki Tanaka Tokyo, Japan More articles by this author Kazunobu Shinoda Tokyo, Japan More articles by this author Hidaka Kono Tokyo, Japan More articles by this author Eiji Kikuchi Tokyo, Japan More articles by this author Hirohiko Nagata Tokyo, Japan More articles by this author Hiroshi Asanuma Tokyo, Japan More articles by this author Akira Miyajima Tokyo, Japan More articles by this author Ken Nakagawa Tokyo, Japan More articles by this author Mototsugu Oya Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...