Dihydrolipoic acid inhibits skin tumor promotion through anti-inflammation and anti-oxidation

Yuan Soon Ho, Ching Shu Lai, Hsin I. Liu, Sheng Yow Ho, Chein Tai, Min Hsiung Pan, Ying Jan Wang

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

α-Lipoic acid (LA) has been intensely investigated as a therapeutic agent for several diseases, including hepatic disorder and diabetic polyneuropathy. However, the effects of LA or its reduced form, dihydrolipoic acid (DHLA), on cancer chemoprevention has never been reported. In the present study, we examined the effects of DHLA/LA on the production of nitric oxide (NO) by inducible NO synthase (iNOS) and the formation of prostaglandin E2 (PGE2) by cyclooxygenase-2 (COX-2), two important mediators associated with inflammation. DHLA/LA significantly inhibited lipopolysaccharide (LPS)-induced NO and PGE2 formation in RAW 264.7 cells. Meanwhile, treatment with DHLA/LA suppressed the expression of iNOS protein but, unexpectedly, did not affect or increase the expression of COX-2 protein. The in vivo anti-inflammatory and antitumor-promoting activities were evaluated by a topical 12-O-tetradecanoylphorbol 13-acetate (TPA) application to mouse skin with measurement of edema formation, epidermal thickness and hydrogen peroxide production. DHLA significantly inhibited the priming and activation stages of skin inflammation induced by a double TPA application, by decreasing the inflammatory parameters. Furthermore, DHLA inhibited DMBA (0.3 μmol)/TPA (2.0 nmol)-induced skin tumor formation by reducing the tumor incidence and tumor multiplicity. When applied topically onto the shaven backs of mice prior to TPA, DHLA markedly inhibited the expression of iNOS protein. DHLA also strongly and directly inhibited COX-2 activity. These results suggest that DHLA can be a possible chemopreventive agent in inflammation-associated tumorigenesis.

Original languageEnglish
Pages (from-to)1786-1795
Number of pages10
JournalBiochemical Pharmacology
Volume73
Issue number11
DOIs
Publication statusPublished - Jun 1 2007

Keywords

  • α-Lipoic acid (LA)
  • Cancer chemoprevention
  • Dihydrolipoic acid (DHLA)
  • Inflammation
  • Oxidative stress
  • Tumor promotion

ASJC Scopus subject areas

  • Pharmacology

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