Modulation of growth and angiogenic potential of oral squamous carcinoma cells in vitro using salvianolic acid B

BMC Complement Altern Med. 2011 Jul 5;11:54. doi: 10.1186/1472-6882-11-54.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Benzofurans / pharmacology
  • Benzofurans / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Leukoplakia
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phytotherapy*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salvia miltiorrhiza / chemistry*
  • Thrombospondins / genetics
  • Thrombospondins / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • Benzofurans
  • Drugs, Chinese Herbal
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Thrombospondins
  • Tumor Necrosis Factor-alpha
  • thrombospondin 2
  • salvianolic acid B
  • Matrix Metalloproteinase 9