Kaempferol suppresses androgen-dependent and androgen-independent prostate cancer by regulating Ki67 expression

Mol Biol Rep. 2022 Jun;49(6):4607-4617. doi: 10.1007/s11033-022-07307-2. Epub 2022 Mar 14.

Abstract

Purpose: Kaempferol is a natural flavonoid that has been reported to be active against many cancers, including prostate cancer, breast cancer and colon cancer. In our previous study, we found kaempferol could act as a selective androgen receptor modulator, thereby suppress development of benign prostatic hyperplasia. This finding inspired us to further explore the effect and the mechanism of action of kaempferol on prostate cancer.

Methods: Plate clone formation assay was performed to detect the effect of kaempferol on cell proliferation. Flow cytometry was used to detect the impact of kaempferol on cell apoptosis and cell cycle distribution. qPCR, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to detect the expression of gene and protein of Ki67 which is a biomarker of cell proliferation.

Results: In the present study, we found kaempferol could dramatically suppress androgen-dependent and androgen-independent prostate cancer cells proliferation and induce their apoptosis. Furthermore, we found that kaempferol induced cell cycle to be arrested at G1 phase in 22Rv1 cells but at S and G2 phase in PC-3 cells. In addition, we detected the mRNA and protein of Ki67 which is corresponding to the cell proliferation and found that kaempferol could significantly inhibit Ki67 expression at mRNA level but increase its expression at protein levels in both androgen-dependent and androgen-independent prostate cancer cells.

Conclusion: Taken together, kaempferol inhibited the proliferation of androgen-dependent and androgen-independent prostate cancer cells by regulating the expression of Ki67. These findings further shed light on the mechanism of action of kaempferol on anti-prostate cancer.

Keywords: Cell apoptosis; Cell proliferation; Kaempferol; Ki67; Prostate cancer.

MeSH terms

  • Androgens* / metabolism
  • Androgens* / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Kaempferols / pharmacology
  • Ki-67 Antigen / genetics
  • Male
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism

Substances

  • Androgens
  • Kaempferols
  • Ki-67 Antigen
  • RNA, Messenger
  • Receptors, Androgen