salvianolic-acid-B and Cell-Transformation--Neoplastic

Our previous studies showed that Salvianolic acid B (Sal B) inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters and such anti-cancer effects might be related to the inhibition of angiogenesis. This study was aimed to further investigate the anti-proliferative effect of Sal B on the most common type of oral cancer, oral squamous cell carcinoma (OSCC) and the possible mechanisms of action with respect to angiogenesis inhibition.. Two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC4, and premalignant leukoplakia cells were treated with different concentrations of Sal B. Cytotoxicity was assessed by MTT assay. cDNA microarray was utilized to evaluate the expression of 96 genes known to be involved in modulating the biological processes of angiogenesis. Real-time reverse transcription-polymerase chain reaction analysis was conducted to confirm the cDNA microarray data.. Sal B induced growth inhibition in OSCC cell lines but had limited effects on premalignant cells. A total of 17 genes showed a greater than 3-fold change when comparing Sal B treated OSCC cells to the control. Among these genes, HIF-1α, TNFα and MMP9 are specifically inhibited, expression of THBS2 was up-regulated.. Sal B has inhibitory effect on OSCC cell growth. The antitumor effect can be attributed to anti-angiogenic potential induced by a decreased expression of some key regulator genes of angiogenesis. Sal B may be a promising modality for treating oral squamous cell carcinoma.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents, Phytogenic; Benzofurans; Carcinoma, Squamous Cell; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Drugs, Chinese Herbal; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leukoplakia; Matrix Metalloproteinase 9; Mouth Neoplasms; Oligonucleotide Array Sequence Analysis; Phytotherapy; Reverse Transcriptase Polymerase Chain Reaction; Salvia miltiorrhiza; Thrombospondins; Tumor Necrosis Factor-alpha; Up-Regulation

Salvia miltiorrhiza (SM) has been used clinically in Asian countries to improve the microcirculation in the human body. Salvianolic acid B (Sal B), a pure compound extracted from SM, has been reported to be effective against fibrosis and ischemia-reperfusion injury, possibly through its anti-lipid peroxidation action. But the effect of Sal B on oral premalignant lesion and oral carcinogenesis remains unexplored. It is our interest to investigate the chemopreventive effect of Sal B on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters with respect to angiogenesis. Seventy male Syrian golden hamsters were randomly divided into five groups, with two of 20 and three of 10. DMBA solution (0.5% in acetone) was applied topically to the left cheek pouch of male Syrian golden hamsters in Groups A and B, while animals in Group C were painted with acetone, three times a week for 6 weeks. For the next 18 weeks, animals in Groups B and D received Sal B daily (10 mg/kg body wt/day) by gavage, animals in Groups A and C received same volume of saline. Animals in Group E received no treatment and served as blank control. At the end of the experiment, animals were killed and tissue samples were collected for histopathological and immunohistochemical examinations. The results showed that Sal B significantly decreased the squamous cell carcinoma (SCC) incidence from 64.7 (11/17) to 16.7% (3/18) (P=0.004); angiogenesis was inhibited in dysplasia and SCC (P<0.01), with a simultaneous decrease in the immunostaining of hypoxia-inducible factor 1alpha and vascular endothelium growth factor protein (P<0.05). The results suggested that Sal B had inhibitory effect against the malignant transformation of oral precancerous lesion and such inhibition may be related to the inhibition of angiogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Oral; Animals; Benzofurans; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chemoprevention; Cricetinae; Male; Mesocricetus; Mouth Neoplasms; Neovascularization, Pathologic; Precancerous Conditions; Random Allocation