- 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 43
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.