PMID- 24133625
OWN - NLM
STAT- MEDLINE
DCOM- 20140519
LR  - 20211203
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Print)
IS  - 2045-7634 (Linking)
VI  - 2
IP  - 1
DP  - 2013 Feb
TI  - Bisebromoamide, an extract from Lyngbya species, induces apoptosis through ERK 
      and mTOR inhibitions in renal cancer cells.
PG  - 32-9
LID - 10.1002/cam4.53 [doi]
AB  - Advanced renal cell carcinoma (RCC) remains an incurable disease, and newer 
      anticancer drugs are needed. Bisebromoamide, a novel cytotoxic peptide, was 
      isolated from the marine cyanobacterium Lyngbya species at our laboratory in 
      2009. This compound specifically inhibited the phosphorylation of ERK in 
      platelet-derived growth factor-activated normal rat kidney cells. The aim of this 
      study was to evaluate the effect and elucidate the potential mechanism of 
      Bisebromoamide actions on human RCC cells. Two renal cancer cell lines, 769-P and 
      786-O, were used. The effects of Bisebromoamide were analyzed employing assays 
      for water-soluble Tetrazolium-1 salts. Apoptosis was determined by flow 
      cytometric TUNEL analysis. Cell-cycle distributions were analyzed by flow 
      cytometry using BrdU/propidium iodide (PI) staining. Kinases of the 
      phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of Rapamycin (mTOR) 
      pathway and Raf/MEK/ERK pathway were analyzed by Western blotting. After 
      Bisebromoamide treatment for 48 and 72 h, cell viability was significantly 
      decreased in both cell lines at 1 and 10 mumol/L. After treatment with 1 mumol/L 
      Bisebromoamide for 72 h, apoptosis and the increased percentage of cells in the 
      sub-G1 phase were observed in both cell lines. Bisebromoamide inhibited the 
      phosphorylation of ERK and Akt in both cell lines tested. Similar effects were 
      demonstrated for phosphorylation of mTOR and p70 S6. Bisebromoamide is a 
      promising potential agent against RCC due to its ability to inhibit both the 
      Raf/MEK/ERK and PI3K/Akt/mTOR pathways.
FAU - Suzuki, Kenjiro
AU  - Suzuki K
AD  - Department of Urology, Keio University School of Medicine 35 Shinanomachi, 
      Shinjuku-ku, Tokyo, 160-8582, Japan.
FAU - Mizuno, Ryuichi
AU  - Mizuno R
FAU - Suenaga, Kiyotake
AU  - Suenaga K
FAU - Teruya, Toshiaki
AU  - Teruya T
FAU - Tanaka, Nobuyuki
AU  - Tanaka N
FAU - Kosaka, Takeo
AU  - Kosaka T
FAU - Oya, Mototsugu
AU  - Oya M
LA  - eng
PT  - Journal Article
DEP - 20130203
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Lyngbya Toxins)
RN  - 0 (Oligopeptides)
RN  - 0 (bisebromoamide)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage/*pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Renal Cell/enzymology/*pathology
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical/methods
MH  - Extracellular Signal-Regulated MAP Kinases/*antagonists & inhibitors/metabolism
MH  - Humans
MH  - Kidney Neoplasms/enzymology/*pathology
MH  - Lyngbya Toxins/pharmacology
MH  - Oligopeptides/administration & dosage/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Tumor Cells, Cultured
PMC - PMC3797566
OTO - NOTNLM
OT  - Akt
OT  - Bisebromoamide
OT  - ERK
OT  - apoptosis
OT  - mTOR
OT  - renal cell carcinoma
EDAT- 2013/10/18 06:00
MHDA- 2014/05/20 06:00
PMCR- 2013/02/01
CRDT- 2013/10/18 06:00
PHST- 2012/08/29 00:00 [received]
PHST- 2012/11/24 00:00 [revised]
PHST- 2012/12/04 00:00 [accepted]
PHST- 2013/10/18 06:00 [entrez]
PHST- 2013/10/18 06:00 [pubmed]
PHST- 2014/05/20 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - 10.1002/cam4.53 [doi]
PST - ppublish
SO  - Cancer Med. 2013 Feb;2(1):32-9. doi: 10.1002/cam4.53. Epub 2013 Feb 3.