Integrating transcriptomics and proteomics to show that tanshinone IIA suppresses cell growth by blocking glucose metabolism in gastric cancer cells
Journal
BMC Genomics
Journal Volume
16
Journal Issue
1
Pages
41
Date Issued
2015
Author(s)
Abstract
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. ? 2014 Lin et al.
SDGs
Other Subjects
adenosine triphosphate; carbohydrate; DNA; glucose; glucose 6 phosphate isomerase; lactate dehydrogenase; lactate dehydrogenase B; lactic acid; RNA; tanshinone IIA; unclassified drug; abietane derivative; glucose; herbaceous agent; tanshinone; transcriptome; tumor protein; AGS cell line; antineoplastic activity; antiproliferative activity; apoptosis; Article; carbohydrate metabolism; cell stress; concentration response; controlled study; cytoskeleton; DNA damage; down regulation; drug mechanism; flow cytometry; G2 phase cell cycle checkpoint; gastric cancer cell line; gene expression regulation; glucose metabolism; growth inhibition; human; human cell; isobaric tags for relative and absolute quantification; next generation sequencing; nutritional deficiency; oncogene; protein analysis; proteomics; RNA sequence; stomach cancer; transcriptomics; upregulation; biosynthesis; cell proliferation; chemistry; drug effects; genetics; metabolism; pathology; Stomach Neoplasms; tumor cell line; Salvia miltiorrhiza; Cell Line, Tumor; Cell Proliferation; Diterpenes, Abietane; Drugs, Chinese Herbal; Gene Expression Regulation, Neoplastic; Glucose; Humans; Neoplasm Proteins; Proteomics; Stomach Neoplasms; Transcriptome
Publisher
BioMed Central Ltd.
Type
journal article