Arctigenin from Fructus Arctii is a novel suppressor of heat shock response in mammalian cells.
Because heat shock proteins (Hsps) are involved in protecting cells and in the pathophysiology of diseases such as inflammation, cancer, and neurodegenerative disorders, the use of regulators of the expression of Hsps in mammalian cells seems to be useful as a potential therapeutic modality. To identify compounds that modulate the response to heat shock, we analyzed several natural products using a mammalian cell line containing an hsp promoterregulated reporter gene. In this study, we found that an extract from Fructus Arctii markedly suppressed the expression of Hsp induced by heat shock. A component of the extract arctigenin, but not the component arctiin, suppressed the response at the level of the activation of heat shock transcription factor, the induction of mRNA, and the synthesis and accumulation of Hsp. Furthermore, arctigenin inhibited the acquisition of thermotolerance in mammalian cells, including cancer cells. Thus, arctigenin seemed to be a new suppressive regulator of heat shock response in mammalian cells, and may be useful for hyperthermia cancer therapy.
Ishihara
Keiichi
K
Department of Biochemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Yamagishi
Nobuyuki
N
Saito
Youhei
Y
Takasaki
Midori
M
Konoshima
Takao
T
Hatayama
Takumi
T
D000818:Animals; D031170:Arctium / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D005663:Furans; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D017705:Lignans; D014157:Transcription Factors; C071942:arctigenin