Bisdemethoxycurcumin suppresses human osteosarcoma U‑2 OS cell migration and invasion via affecting the PI3K/Akt/NF‑κB, PI3K/Akt/GSK3β and MAPK signaling pathways in vitro

Oncol Rep. 2022 Dec;48(6):210. doi: 10.3892/or.2022.8425. Epub 2022 Oct 12.

Abstract

The metastasis of human osteosarcoma (OS) shows a difficult‑to‑treat clinical scenario and results in decreased quality of life and diminished survival rates. Finding or developing novel treatments to improve the life quality of patients is urgent. Bisdemethoxycurcumin (BDMC), a natural product, was obtained from the rhizome of turmeric (Curcuma longa) and exerts antitumor activities in numerous human cancer cell lines. At present, there is no study showing BDMC effects on OS cell migration and invasion. In the present study, the effects of BDMC on cell migration and invasion of OS U‑2 OS cells were investigated in vitro. Cell viability and proliferation were measured by flow cytometric and MTT assays, respectively. Cell motility, MMP‑2 and ‑9 activity, and cell migration and invasion were assayed by scratch wound healing, gelatin zymography, and Transwell chamber assays, respectively. The protein expression levels were measured by western blotting. BDMC at 20 and 40 µM significantly reduced total cell viability, and BDMC at 5 and 10 µM significantly inhibited cell motility in U‑2 OS cells. BDMC significantly suppressed the activities of MMP‑2 and MMP‑9 in U‑2 OS cells. BDMC suppressed cell invasion and migration after 24 h treatment in U‑2 OS cells, and these effects were in a dose‑dependently manner. Results from western blotting indicated that BDMC significantly decreased the protein expression levels of PI3K/Akt/NF‑κB, PI3K/Akt/GSK3β, and MAPK pathway in U‑2 OS cells. Furthermore, BDMC inhibited uPA, MMP‑2, MMP‑9, MMP‑13, N‑cadherin, VE‑cadherin, and vimentin but increased E‑cadherin in U‑2 OS cells. Based on these observations, it was suggested that BDMC may be a potential candidate against migration and invasion of human OS cells in the future.

Keywords: MAPK; PI3K/Akt/GSK3β; PI3K/Akt/NF‑κB; bisdemethoxycurcumin; cell migration and invasion; human osteosarcoma cells.

MeSH terms

  • Biological Products* / pharmacology
  • Bone Neoplasms* / pathology
  • Cadherins
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Diarylheptanoids
  • Gelatin / pharmacology
  • Gelatin / therapeutic use
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Osteosarcoma* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quality of Life
  • Signal Transduction
  • Vimentin / metabolism

Substances

  • Biological Products
  • Cadherins
  • Diarylheptanoids
  • NF-kappa B
  • Vimentin
  • bisdemethoxycurcumin
  • Gelatin
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9