The effect of Apigenin on glycometabolism and cell death in an anaplastic thyroid cancer cell line

Toxicol Appl Pharmacol. 2023 Sep 15:475:116626. doi: 10.1016/j.taap.2023.116626. Epub 2023 Jul 10.

Abstract

Aims and background: A more pronounced characteristic of cancer cells is the energy dependence on glucose, which mitigated by glucose transporters. The comprehension of the regulatory mechanisms behind the Warburg effect holds promise for developing therapeutic interventions for cancers. Studies are lacking which targeted the GLUTs for treatment of malignancy of thyroid tumors. In our current investigation, we have undertaken this study to determine the potential of Apigenin, plant derived flavonoid in modulating tumor apoptosis by targeting GLUTs expression in SW1736 cell line of anaplastic thyroid carcinoma.

Material methods: Flow cytometry with propidium iodide staining was used to determine cell apoptosis. For glucose uptake detection, the "GOD-PAP" enzymatic colorimetric test was used to measure the direct glucose levels inside the cells. To determine the expression of GLUT1 and GLUT3 mRNA in the SW1736 cell line qRT-PCR was employed. Protein levels of GLUT1 and GLUT3 in the SW1736 cell line were detected with western blotting. Also, the scratch wound healing assay was conducted for cell migration.

Results: According to qRT-PCR analysis, the levels of GLUT1 and GLUT3 mRNA were lower in the group that received Apigenin relative to the control group. The Apigenin treatment of SW1736 cells decreased protein expression of the GLUT1 and GLUT3 levels in conformity to qRT-PCR. The scratch assays revealed that Apigenin treatment of cancer cell lines inhibited cell migration as compared to control.

Conclusion: These findings demonstrate the possibility of targeting the glucose facilitators' pathway for making thyroid cancer cells more susceptible to programmed cell death.

Keywords: Anaplastic thyroid cancer; Apigenin; Apoptosis; Glucose transporter; Glucose uptake; Programmed cell death.

MeSH terms

  • Apigenin / pharmacology
  • Apigenin / therapeutic use
  • Apoptosis
  • Cell Line
  • Cell Line, Tumor
  • Glucose
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 3 / genetics
  • Humans
  • RNA, Messenger
  • Thyroid Carcinoma, Anaplastic* / drug therapy
  • Thyroid Carcinoma, Anaplastic* / pathology
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / pathology

Substances

  • Apigenin
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Glucose
  • RNA, Messenger