1,2,3-Triazolyl ester of ketorolac (15K): boosting both heat-endurance and lifespan of C. elegans by down-regulating PAK1 at nM levels
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- Nguyen Binh C.
- PAK Research Center
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- Kim Sung-A
- Soonchunhyang University
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- Won Seong-Min
- Soonchunhyang University
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- Park Sang-Kyu
- Soonchunhyang University
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- Uto Yoshihiro
- Tokushima University
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- Maruta Hiroshi
- PAK Research Center
書誌事項
- タイトル別名
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- 1,2,3-Triazolyl ester of ketorolac (15K): Boosting both heat-endurance and lifespan of <i>C. elegans</i> by down-regulating PAK1 at nM levels
抄録
<p>PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic/ageing kinase, and its dysfunction extends the healthy lifespan of C. elegans by activating HSP16 gene. 15K is a highly cell-permeable 1,2,3-triazolyl ester of ketorolac that down-regulates both PAK1 and its down-stream COX-2 in R- and S-forms, respectively. 15K is 500-5,000 times more potent than ketorolac, an old pain-killer, inhibiting the growth of cancer cell lines with IC50 ranging 5-24 nM. Scores of natural and synthetic PAK1-blockers have been shown to extend the lifespan of small animals such as C. elegans, but none of them has been effective at nM levels. Thus, we examined in vivo effect of 15K at nM levels on the survival rate of C. elegans with or without heat-shock. Like the PAK1-deficient mutant, 15K (at 50 nM)-treated worm significantly lives longer, is far more heat-resistant and less productive (fertile) than the non-treated counterpart, with an increased expression of HSP16 gene. 15K has been proven to be among the most potent anti-cancerous and longevity-promoting PAK1-blockers, and therefore has a potential to treat a variety of solid tumours without severe side effect.</p>
収録刊行物
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- Drug Discoveries & Therapeutics
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Drug Discoveries & Therapeutics 12 (2), 92-96, 2018-04-30
特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会