Chemical inducers of heat shock proteins derived from medicinal plants and cytoprotective genes response

Kanwal Ahmed, Yukihiro Furusawa, Yoshiaki Tabuchi, Heba F. Emam, Jin Lan Piao, Mariame Ali Hassan, Takeshi Yamamoto, Takashi Kondo, Makoto Kadowaki

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Environmental stress induces damage that activates an adaptive response in any organism. The cellular stress response is based on the induction of cytoprotective proteins, the so-called stress or heat shock proteins (HSPs). HSPs are known to function as molecular chaperones which are involved in the therapeutic approach of many diseases. Therefore in the current study we searched nontoxic chaperone inducers in chemical compounds isolated from medicinal plants. Screening of 80 compounds for their Hsp70-inducing activity in human lymphoma U937 cells was performed by western blotting. Five compounds showed significant Hsp70 up-regulation among them shikonin was most potent. Shikonin was able to induce Hsp70 at 0.1μM after 3h without activation of heat shock transcription factor 1 (HSF-1). It also induces significant reactive oxygen species generation. The expression level of genes responsive to shikonin was studied using global-scale microarrays and computational gene expression analysis tools. Significant increase in the nuclear factor erythroid 2-related factor 2 (Nrf2, NFEL2L2) -mediated oxidative stress response was observed that leads to the activation of HSP. The results of gene chip analysis were further confirmed by real-time qPCR assay. In short, the detailed mechanisms of Hsp70 induction by shikonin is not fully understood, Nrf2 and its target genes might be involved in the Hsp70 up-regulation in U937 cells.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalInternational Journal of Hyperthermia
Volume28
Issue number1
DOIs
Publication statusPublished - 2012 Feb 1

Keywords

  • Heat shock proteins
  • Nrf2
  • oxidative stress
  • shikonin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cancer Research

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    Ahmed, K., Furusawa, Y., Tabuchi, Y., Emam, H. F., Piao, J. L., Hassan, M. A., Yamamoto, T., Kondo, T., & Kadowaki, M. (2012). Chemical inducers of heat shock proteins derived from medicinal plants and cytoprotective genes response. International Journal of Hyperthermia, 28(1), 1-8. https://doi.org/10.3109/02656736.2011.627408