Tanshinone IIA inhibits glucose metabolism leading to apoptosis in cervical cancer

Oncol Rep. 2019 Nov;42(5):1893-1903. doi: 10.3892/or.2019.7294. Epub 2019 Aug 27.

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.

MeSH terms

  • Abietanes / administration & dosage*
  • Abietanes / pharmacology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Glucose / metabolism*
  • HeLa Cells
  • Humans
  • Lactic Acid / metabolism
  • Mice
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Abietanes
  • Antineoplastic Agents, Phytogenic
  • tanshinone
  • Lactic Acid
  • Adenosine Triphosphate
  • Glucose