Metabolic transformation of DMBA-induced carcinogenesis and inhibitory effect of salvianolic acid B and breviscapine treatment

Jie Wei, Guoxiang Xie, Shuyun Ge, Yunping Qiu, Wei Liu, Aiping Lu, Tianlu Chen, Houkai Li, Zengtong Zhou, Wei Jia

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31 Scopus citations

Abstract

Oral cancer typically develops from hyperplasia through dysplasia to carcinoma with a multistep process of carcinogenesis involving genetic alterations resulting in aberrant cellular appearance, deregulated cell growth, and carcinoma. The metabolic transformation during the process of oral carcinogenesis and its implications for cancer therapy have not been extensively investigated. Here, we report a metabonomic study on a classical model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced oral carcinogenesis in hamsters to delineate characteristic metabolic transformation during the carcinogenesis using gas chromatography time-of-flight mass spectrometry (GC-TOF MS). Salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, and Breviscapine, a flavonoid isolated from Herba Erigerontis, were used to treat the hamsters exposed to DMBA to investigate the molecular mechanism of the inhibitory effect of the two agents on oral carcinogenesis. The dynamic changes of serum metabolic profiles indicated that both Sal-B and Breviscapine were able to attenuate DMBA-induced metabolic perturbation, which is consistent with the histopathological findings that Sal-B and Breviscapine significantly decreased the squamous cell carcinoma (SCC) incidence in the two treatment groups. Significant alterations of key metabolic pathways, including elevated glutaminolysis and glycolysis, and decreased cholesterol and myo-inositol metabolism, were observed in the DMBA-induced model group, which were attenuated or normalized by Sal-B or Breviscapine treatment. Elevated inflammation and tumor angiogenesis at gene and metabolite expression levels were also observed in DMBA-induced oral dysplasia and SCC but were attenuated or normalized by Sal-B and Breviscapine along with significantly decreased incidences of SCC formation.

Original languageEnglish (US)
Pages (from-to)1302-1316
Number of pages15
JournalJournal of Proteome Research
Volume11
Issue number2
DOIs
StatePublished - Feb 3 2012
Externally publishedYes

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Keywords

  • 7,12-dimethylbenz(a)anthracene
  • Breviscapine
  • DMBA
  • GC-TOF MS
  • Salvianolic acid B
  • angiogenesis
  • carcinogenesis
  • gas chromatography time-of-flight mass spectrometry
  • metabonomics
  • oral cancer

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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