Integrating transcriptomics and proteomics to show that tanshinone IIA suppresses cell growth by blocking glucose metabolism in gastric cancer cells

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• 作者：Li-Ling Lin (1)
  Chieh-Ren Hsia (1)
  Chia-Lang Hsu (1)
  Hsuan-Cheng Huang (2)
  Hsueh-Fen Juan (1) (3) (4)
  
  1. Department of Life Science ; National Taiwan University ; No. 1 ; Sec. 4 ; Roosevelt Road ; Taipei ; 106 ; Taiwan
  2. Institute of Biomedical Informatics and Center for Systems and Synthetic Biology ; National Yang-Ming University ; No.155 ; Sec.2 ; Linong Street ; Taipei ; 112 ; Taiwan
  3. Institute of Molecular and Cellular Biology ; National Taiwan University ; No. 1 ; Sec. 4 ; Roosevelt Road ; Taipei ; 106 ; Taiwan
  4. Graduate Institute of Biomedical Electronics and Bioinformatics ; National Taiwan University ; No. 1 ; Sec. 4 ; Roosevelt Road ; Taipei ; 106 ; Taiwan
  
• 关键词：Tanshinone IIA ; Gastric cancer ; Glycolysis ; Isobaric tags for relative and absolute quantification ; Next generation sequencing
• 刊名：BMC Genomics
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：16
• 期：1
• 全文大小：2,269 KB
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• 刊物主题：Life Sciences, general; Microarrays; Proteomics; Animal Genetics and Genomics; Microbial Genetics and Genomics; Plant Genetics & Genomics;
• 出版者：BioMed Central
• ISSN：1471-2164

文摘

Background Tanshinone IIA (TIIA) is a diterpene quinone extracted from the plant Danshen (Salvia miltiorrhiza) used in traditional Chinese herbal medicine. It has been reported to have anti-tumor potential against several kinds of cancer, including gastric cancer. In most solid tumors, a metabolic switch to glucose is a hallmark of cancer cells, which do this to provide nutrients for cell proliferation. However, the mechanism associated with glucose metabolism by which TIIA acts on gastric cancer cells remains to be elucidated. Results We found that TIIA treatment is able to significantly inhibit cell growth and the proliferation of gastric cancer in a dose-dependent manner. Using next-generation sequencing-based RNA-seq transcriptomics and quantitative proteomics-isobaric tags for relative and absolute quantification (iTRAQ), we characterized the mechanism of TIIA regulation in gastric cancer cell line AGS. In total, 16,603 unique transcripts and 102 proteins were identified. After enrichment analysis, we found that TIIA regulated genes are involved in carbohydrate metabolism, the cell cycle, apoptosis, DNA damage and cytoskeleton reorganization. Our proteomics data revealed the downregulation of intracellular ATP levels, glucose-6-phosphate isomerase and L-lactate dehydrogenase B chains by TIIA, which might work with disorders of glucose metabolism and extracellular lactate levels to suppress cell proliferation. The up-regulation of p53 and down-regulation of AKT was shown in TIIA- treated cells, which indicates the transformation of oncogenes. Severe DNA damage, cell cycle arrest at the G2/M transition and apoptosis with cytoskeleton reorganization were detected in TIIA-treated gastric cancer cells. Conclusions Combining transcriptomics and proteomics results, we propose that TIIA treatment could lead cell stresses, including nutrient deficiency and DNA damage, by inhibiting the glucose metabolism of cancer cells. This study provides an insight into how the TIIA regulatory metabolism in gastric cancer cells suppresses cell growth, and may help improve the development of cancer therapy.