著者
Binh Cao Quan Nguyen Kazuki Yoshimura Shigenori Kumazawa Shinkichi Tawata Hiroshi Maruta
出版者
International Research and Cooperation Association for Bio & Socio-Sciences Advancement
雑誌
Drug Discoveries & Therapeutics (ISSN:18817831)
巻号頁・発行日
vol.11, no.2, pp.110-114, 2017-04-30 (Released:2017-05-30)
参考文献数
13
被引用文献数
36 44

A sulfated saponin called "Frondoside A" (FRA) from sea cucumber and ingredients from Okinawa propolis (OP) have been previously shown to suppress the PAK1-dependent growth of A549 lung cancer as well as pancreatic cancer cells. However, the precise molecular mechanism underlying their anti-cancer action still remains to be clarified. In this study, for the first time, we found that both FRA and OP directly inhibit PAK1 in vitro in a selective manner (far more effectively than two other oncogenic kinases, LIMK and AKT). Furthermore, at least two major anti-cancer ingredients of OP, nymphaeols A and C, also directly inhibit PAK1 in vitro in a selective manner. To the best of our knowledge, FRA is the first marine compound that selectively inhibits PAK1. Likewise, these nymphaeols are the first propolis ingredients that selectively inhibit PAK1.
著者
Hiroshi Maruta Mok-Ryeon Ahn
出版者
International Research and Cooperation Association for Bio & Socio-Sciences Advancement
雑誌
Drug Discoveries & Therapeutics (ISSN:18817831)
巻号頁・発行日
vol.16, no.1, pp.43-46, 2022-02-28 (Released:2022-03-09)
参考文献数
35

PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type. Interestingly, PAK1-deficient mutant of melanocytes produces less melanin (only a half compared with the wild-type) in the presence of either serum (PDGF) or α-MSH (alpha-melanocyte stimulating hormone). These observations indicate that the major "pathogenic" kinase PAK1 is responsible for both shortening the healthy lifespan, and PDGF/α-MSH-dependent melanogenesis. For screening of PAK1-blocking probiotic bacteria or their products, their anti-melanogenic as well as longevity promoting properties were examined. Recently it was found that C. elegans fed with Lactobacillus rhamnosus in Xinjiang cheese lives 40% longer than the worm fed with the standard E. coli. Interestingly, a Chinese traditional medicine called "ChiBai" fermented with the Lactobacillus rhamnosus also inhibited the α-MSH-induced melanogenesis, and this bacteria itself produces butyric acid that blocks the oncogenic HDAC (histone deacetylase)-PAK1 signaling pathway. These findings strongly suggest, if not proven, that anti-melanogenic activity of Lactobacillus and many other probiotic bacteria might serve as a reliable indicator for their longevity promoting activity. In this context, a popular Japanese Lactobacillus-fermented milk drink called "Calpis", developed a century ago, and recently proven to inhibit the melanogenesis by suppressing the PAK1-dependent tyrosinase gene expression, may potentially prolong our healthy lifespan.