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Tanshinone IIA inhibits glucose metabolism leading to apoptosis in cervical cancer.

ABSTRACT: Cancer requires aerobic glycolysis to supply the energy required for proliferation. Existing evidence has revealed that blocking glycolysis results in apoptosis of cancer cells. Tanshinone IIA (Tan IIA) is a diterpenoid naphthoquinone found in traditional Chinese medicine, Danshen (Salvia sp.). Tan IIA exhibits potential anticancer activity. However, its effect on cell viability of human cervical cancer cells and its mechanism are unknown. The aim of the present study was to determine the effect of Tan IIA on proliferation and glucose metabolism in cervical cancer cells. Cell viability was measured by MTT assay, apoptosis was determined using flow cytometry and glucose uptake, lactate production, and adenosine triphosphate content were measured to assess glucose metabolism. The expression of apoptosis‑associated proteins was detected by western blotting and the antitumor activity of Tan IIA in vivo was evaluated in cervical carcinoma‑bearing mice. The results revealed Tan IIA treatment resulted in a considerable reduction in the viability of SiHa cells. Tan IIA decreased the expression of HPV oncogenes E6 and E7, induced apoptosis and also decreased glycolysis by suppressing the activity of the intracellular AKT/mTOR and HIF‑1α. In vivo, treatment with Tan IIA resulted in a 72.7% reduction in tumor volume. The present study highlights the potential therapeutic value of Tan IIA, which functions by inducing apoptosis and may be associated with inhibition of glycolysis.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6775814 | biostudies-other | 2019 Aug

REPOSITORIES: biostudies-other

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Tanshinone IIA inhibits glucose metabolism leading to apoptosis in cervical cancer.

Liu Zhigang Z Zhu Wenhe W Kong Xiangyu X Chen Xi X Sun Xinyi X Zhang Wei W Zhang Ruowen R

Oncology reports 20190827 5

Cancer requires aerobic glycolysis to supply the energy required for proliferation. Existing evidence has revealed that blocking glycolysis results in apoptosis of cancer cells. Tanshinone IIA (Tan IIA) is a diterpenoid naphthoquinone found in traditional Chinese medicine, Danshen (Salvia sp.). Tan IIA exhibits potential anticancer activity. However, its effect on cell viability of human cervical cancer cells and its mechanism are unknown. The aim of the present study was to determine the effect ...[more]

PMID: 31485631

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Project description: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.

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Tanshinone IIA inhibits glucose metabolism leading to apoptosis in cervical cancer.

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Tanshinone IIA inhibits glucose metabolism leading to apoptosis in cervical cancer.

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