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

Abstract

BackgroundTanshinone 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.ResultsWe 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.ConclusionsCombining 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1230-0) contains supplementary material, which is available to authorized users.

Tanshinone IIA inhibits the proliferation, migration and invasion of ectopic endometrial stromal cells of adenomyosis via 14-3-3ζ downregulation

“…In this study, we found that TSIIA decreased significantly the cell viability of EESCs in a dose-dependent manner, and 20 lL of TSIIA could result in obviously decreased cell viability; this is similar to recent observations that TSIIA could inhibit multiple cancer cells proliferation [20,36,37]. Furthermore, overexpression of 14-3-3f could restore cell viability of TSIIA-treated EESCs, implying that the inhibitory effect of cell viability was mediated by 14-3-3f.…”

“…In recent years, multiple studies have shown that TSIIA has therapeutic effects on different types of cancers, exhibiting with decreased cell viability, increased cell apoptosis, inhibition of cell invasion and migration [19,20]. The potential therapeutic mechanisms might be versatile, including inhibition of DNA synthesis and increased cell apoptosis [19,35].…”

“…TSIIA was initially used mainly in the treatment of cardiovascular diseases, such as hypertension, atherosclerosis and dyslipidemia [16][17][18]; subsequent studies also revealed that it had good curative effect in other disorders, including cancer [19,20], polycystic ovary syndrome [21] and endometriosis [22]. Till now, although great progress has been made, the detailed molecular mechanisms underlying TSIIA therapeutic effects remained largely unclear, especially in non-cardiovascular diseases.…”

Introduction to Cancer Systems Biology

“…The cancer systems biology approach is very effective in identifying drug targets, developing novel therapeutics and new indications for existing drugs. [7][8][9][10] In addition to target and drug discovery, cancer systems biology represents a valuable contribution to efforts toward understanding the molecular mechanism of drugs in various cancer types 5,11 and regulation in cancer progression. 4 …”

“…For example, tanshinone IIA (TIIA) is a diterpene quinone extracted from the plant Danshen (Salvia miltiorrhiza), which is used in traditional Chinese medicine. 11,25 By analyzing RNA-sequencing and proteome data in TIIA-treated gastric cancer cells, TIIA was found to suppress cell growth by blocking glucose metabolism. 11…”