@article{f46bbc6e3d9a45b3a72b33e1379460aa,
title = "Identification of protein kinase C isozymes involved in the anti-proliferative and pro-apoptotic activities of 10-Methyl-aplog-1, a simplified analog of debromoaplysiatoxin, in several cancer cell lines",
abstract = "10-Me-aplog-1 is a simplified analog of the tumor-promoting compound debromoaplysiatoxin (DAT) and a unique protein kinase C (PKC) activator with limited tumor-promoting and pro-inflammatory activities. 10-Me-aplog-1 inhibits the growth of several cancer cell lines, but the inhibitory mechanism involving PKC isozymes remains unclear. We quantified the amount of PKC isozymes in nine human cancer cell lines that differ in 10-Me-aplog-1 sensitivity. PKCα and δ were the predominant isozymes expressed in all cell lines, but there was no significant correlation between expression levels and anti-proliferative activity. Knocking down PKCα, and/or PKCδ in the three aplog-sensitive cell lines indicated their involvement in the anti-proliferative and pro-apoptotic activities of 10-Me-aplog-1. This finding suggests that PKCα and/or PKCδ activation could be effective for treating certain cancers. Since the mechanism underlying 10-Me-aplog-1's anti-proliferative activities resembles that of DAT, 10-Me-aplog-1 may be regarded as a special key derived from pleiotropic DAT as a bunch of keys.",
keywords = "Aplysiatoxin, Phorbol ester, Protein kinase C, Tumor promoter",
author = "Yusuke Hanaki and Yuki Shikata and Masayuki Kikumori and Natsuki Hotta and Masaya Imoto and Kazuhiro Irie",
note = "Funding Information: We thank Professor Hiroshi Nagai of the Department of Ocean Science at Tokyo University of Marine Science and Technology, and Professor Kiyotake Suenaga of the Faculty of Science and Technology at Keio University for the supply of debromoaplysiatoxin. This work was partly supported by a Grant-in-Aid for Scientific Research on Innovative Areas 'Frontier Research on Chemical Communications' (No. 17H06405 to K.I.) and a Grant-in-Aid for the Promotion of Science for Young Scientists (No. 16J04817 to Y.H.) from the Japanese government (Monbukagakusho: MEXT). Funding Information: We thank Professor Hiroshi Nagai of the Department of Ocean Science at Tokyo University of Marine Science and Technology, and Professor Kiyotake Suenaga of the Faculty of Science and Technology at Keio University for the supply of debromoaplysiatoxin. This work was partly supported by a Grant-in-Aid for Scientific Research on Innovative Areas 'Frontier Research on Chemical Communications' (No. 17H06405 to K.I.) and a Grant-in-Aid for the Promotion of Science for Young Scientists (No. 16J04817 to Y.H.) from the Japanese government (Monbukagakusho: MEXT). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2018",
month = jan,
day = "1",
doi = "10.1016/j.bbrc.2017.11.052",
language = "English",
volume = "495",
pages = "438--445",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",
}
