Combination of Kaempferol and Docetaxel Induces Autophagy in Prostate Cancer Cells In Vitro and In Vivo

Int J Mol Sci. 2023 Sep 25;24(19):14519. doi: 10.3390/ijms241914519.

Abstract

Docetaxel is a first-line chemotherapy drug used to treat advanced prostate cancer, but patients who have used it often face the challenges of drug resistance and side effects. Kaempferol is a naturally occurring flavonol; our previous studies have confirmed that it has excellent anti-prostate activity. To investigate the anti-prostate cancer effects of docetaxel in combination with kaempferol, we conducted experiments at the cellular and whole-animal level. Plate cloning assays showed that the combination of docetaxel and kaempferol had a synergistic effect in inhibiting the proliferation of prostate cancer cells. The combination of these two compounds was found to induce autophagy in prostate cancer cells via transmission electron microscopy, and changes in the expression of autophagy-related proteins via Western blot assays also confirmed the occurrence of autophagy at the molecular level. We also confirmed the anti-prostate cancer effect of docetaxel in combination with kaempferol in vivo by establishing a mouse xenograft prostate cancer model. Autophagy-related proteins were also examined in mouse tumor tissues and verified the presence of autophagy in mouse tumor tissues. The above cellular and animal data suggest that docetaxel in combination with kaempferol has significant anti-prostate cancer effects and that it works by inducing autophagy in cells.

Keywords: autophagy; combined treatment; docetaxel; kaempferol; prostate cancer.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy
  • Autophagy-Related Proteins
  • Cell Line, Tumor
  • Docetaxel / pharmacology
  • Docetaxel / therapeutic use
  • Humans
  • Kaempferols* / pharmacology
  • Kaempferols* / therapeutic use
  • Male
  • Mice
  • Prostatic Neoplasms* / metabolism
  • Taxoids / pharmacology
  • Taxoids / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Docetaxel
  • Kaempferols
  • Taxoids
  • Autophagy-Related Proteins