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Anti-tumor effects of metformin: Effects of metformin on Sirt1, Nrf2 and AhR expression in cancer cells

Anti-tumor effects of metformin: Effects of metformin on Sirt1, Nrf2 and AhR expression in cancer cells

정혜광 ( Hye Gwang Jeong )

- 발행기관 : 전남대학교 약품개발연구소

- 발행년도 : 2016

- 간행물 : 약품개발연구지, 25권 0호

- 페이지 : pp.147-152 ( 총 6 페이지 )


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논문제목
초록(외국어)
The expression of Sirt1, Nrf2 and AhR relates to tumorigenesis, chemoresistance and carcinogenesis. Accumulating evidence suggests that metformin has antitumor activity. This study investigated effects of metformin on expression of Sirt1, Nrf2, AhR and its downstream target genes in cancer cells. Results indicated that metformin down-regulated the constitutive and inducible expression of CYP1A1 and CYP1B1 in MCF-7 and MDA-MB-231 breast cancer cells. Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression. Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing TDO expression. Moreover, metformin strongly suppresses HO-1 expression in A549 cancer cells. Metformin also markedly reduced Nrf2 activation and expression. The regulation of Nrf2 expression by metformin is mediated through a Keap1-independent mechanism and that the reduction. of Nrf2 expression is mediated by an attenuation of Raf-ERK signaling by metformin. Additionally, metformin induced p53 protein levels in wild-type p53 cancer cells resulted in up-regulation of miR-34a and down-regulation of Sirt1. Genetic tools demonstrated that the reduction of Sirt1 and Pgc-1α by metformin caused Nrf2 down-regulation via suppression of PPARγ transcriptional activity. The Sirt1 reduction by metformin increased DR5 expression. Metformin pretreatment enhanced the susceptibility of cancer cells to oxidative stress and TRAIL-induced apoptosis. These results demonstrated that metformin down-regulates Sirt1, Nrf2 and AhR expression in cancer cells following with correlative pharmacological activities. Metformin is commonly used for type 2 diabetes. Therefore, metformin may be an effective therapy for the cancer prevention and treatment.

논문정보
  • - 주제 : 의약학분야 > 약품제제
  • - 발행기관 : 전남대학교 약품개발연구소
  • - 간행물 : 약품개발연구지, 25권 0호
  • - 발행년도 : 2016
  • - 페이지 : pp.147-152 ( 총 6 페이지 )
  • - UCI(KEPA) : I410-ECN-0102-2018-500-000236199
저널정보
  • - 주제 : 의약학분야 > 약품제제
  • - 성격 : 학술지
  • - 간기 : 연간
  • - 국내 등재 : -
  • - 해외 등재 : -
  • - ISSN :
  • - 수록범위 : 1995–2016
  • - 수록 논문수 : 731