Curcumol inhibits the malignant progression of prostate cancer and regulates the PDK1/AKT/mTOR pathway by targeting miR‑9

Oncol Rep. 2021 Nov;46(5):246. doi: 10.3892/or.2021.8197. Epub 2021 Sep 30.

Abstract

Curcumol has been reported to exert anti‑tumor activity, but its intrinsic molecular mechanism in prostate cancer remains to be elucidated. The present study aimed to analyze the effect of curcumol on prostate cancer and identify its possible internal regulatory pathway using in vitro cell culture and in vivo tumor model experiments. The cytotoxicity of curcumol was detected using a Cell Counting Kit‑8 assay and it was found that curcumol had no obvious toxicity or side effects on RWPE‑1 cells. Wound healing, Transwell and flow cytometry assays demonstrated that curcumol could affect the activity of PC3 cells. The luciferase reporter assay also indicated that microRNA (miR)‑9 could directly target pyruvate dehydrogenase kinase 1 (PDK1). After PC3 cells were transfected with miR‑9 inhibitor or treated with curcumol, the expression levels of the PDK1/AKT/mTOR signaling pathway‑related proteins [PDK1, phosphorylated (p)‑AKT and p‑mTOR] were increased or decreased, respectively. Next, the prostate cancer cell xenograft model was established. Tumor size and the expression levels of PDK1/AKT/mTOR signaling pathway‑related factors were altered following treatment with curcumol. The in vitro and in vivo experiments collectively demonstrated that curcumol could inhibit the PDK1/AKT/mTOR signaling pathway by upregulating the expression level of miR‑9. The present study found that curcumol regulates the PDK1/AKT/mTOR signaling pathway via miR‑9 and affects the development of prostate cancer. These findings could provide a possible scientific insight for research into treatments for prostate cancer.

Keywords: curcumol; microRNA‑9; prostate cancer; pyruvate dehydrogenase kinase 1/AKT/mTOR pathway.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • PC-3 Cells
  • Prostatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase / metabolism*
  • Sesquiterpenes / pharmacology*
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation

Substances

  • MIRN92 microRNA, human
  • MicroRNAs
  • PDK1 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Sesquiterpenes
  • curcumol
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Grants and funding

This work was supported by the National Natural Science Foundation (grant no. 81774324), and the Postgraduate Innovation Project of Hunan Province (grant no. CX2018B463).