title: Metabolic transformation of DMBA-induced carcinogenesis and inhibitory effect of salvianolic acid b and breviscapine treatment.
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.
authors: Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.
authors: Jie
authors: J
authors: Wei
authors: Guoxiang
authors: G
authors: Xie
authors: Shuyun
authors: S
authors: Ge
authors: Yunping
authors: Y
authors: Qiu
authors: Wei
authors: W
authors: Liu
authors: Aiping
authors: A
authors: Lu
authors: Tianlu
authors: T
authors: Chen
authors: Houkai
authors: H
authors: Li
authors: Zengtong
authors: Z
authors: Zhou
authors: Wei
authors: W
authors: Jia
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D006224:Cricetinae; D004347:Drug Interactions; D005419:Flavonoids / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006651:Histocytochemistry; D008297:Male; D008647:Mesocricetus; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects; D055432:Metabolomics; D009062:Mouth Neoplasms / Q000098:blood supply / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D053630:Depsides
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D001572:Benzofurans; D002273:Carcinogens; D005419:Flavonoids; C061097:breviscapine; C076944:salvianolic acid B; D053630:Depsides