Astragalin induced selective kidney cancer cell death and these effects are mediated via mitochondrial mediated cell apoptosis, cell cycle arrest, and modulation of key tumor-suppressive miRNAs

J BUON. 2019 May-Jun;24(3):1245-1251.

Abstract

Purpose: Kidney cancer is responsible for a significant number of deaths worldwide. This cancer is often diagnosed at advanced stages and there are frequent relapses following chemotherapy. Target therapies are used now for kidney cancer, while the use of chemotherapy declines. The currently used chemotherapeutic drugs have a number of adverse effects. Herein, we examined the anticancer effects of Astragalin against a panel of kidney cancer cells.

Methods: CellTiter-Glo Luminescent Cell Viability Assay Kit was used to examine the anti-proliferative effects of Astragalin. Acridine orange (AO)/ethidium bromide (EB), DAPI and annexin V/promidium iodide (PI) staining assays were used to examine the apoptotic cell death. Cell cycle analysis was performed by flow cytometry. The mRNA expression was checked by qRT-PCR and protein expression was examined by western blotting.

Results: Astragalin inhibited the growth of the all kidney cancer cell lines with IC50 ranging between 20 to 50 µM. Of note, Astragalin had low cytotoxic effects on the normal kidney cells with an IC50 of 110 µM. The experiments have shown that Astragalin exerts antiproliferative effects on the A498 kidney cancer cells by apoptotic cell death. This effect was concomitant with upregulation of apoptotic proteins such as caspase 3 and 9 and Bax. Astragalin also induced arrest of the A498 cells at the G2/M checkpoint of the cell cycle. Also, Astragalin could upregulate the expression of tumor-suppressive microRNAs.

Conclusions: These results suggest that Astragalin exerts potent anticancer effects on kidney cancer cells and could pave the way in the management of kidney cancer provided clinical studies are carried out.

MeSH terms

  • Apoptosis
  • Carcinoma, Renal Cell / chemically induced*
  • Carcinoma, Renal Cell / pathology
  • Cell Cycle Checkpoints
  • Cell Death
  • Cell Line, Tumor
  • Humans
  • Kaempferols / adverse effects*
  • Kaempferols / pharmacology
  • MicroRNAs / metabolism*
  • Mitochondria

Substances

  • Kaempferols
  • MicroRNAs
  • astragalin