LQB-118 Suppresses Migration and Invasion of Prostate Cancer Cells by Modulating the Akt/GSK3β Pathway and MMP-9/Reck Gene Expression

  • Anticancer Res. 2023 Jan;43(1):359-367. doi: 10.21873/anticanres.16171.
Thiago Martino  1 ,  Graziele Freitas DE Bem  2 ,  Shirley Vania Moura Santos  1 ,  Marsen Garcia Pinto Coelho  1 ,  Angela DE Castro Resende  2 ,  Chaquip Netto  3 ,  Paulo Roberto Ribeiro Costa  3 ,  Graça Justo  4 ,  Katia Costa DE Carvalho Sabino  1
Affiliations
  • 1. LIA-BPPN, Department of Biochemistry, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • 2. Department of Pharmacology, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • 3. IPPN, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • 4. LIA-BPPN, Department of Biochemistry, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil; [email protected].
PMID: 36585169 DOI: 10.21873/anticanres.16171
Abstract

Background/aim: Prostate Cancer (PCa) is one of the most common malignancies in adult men. LQB-118 is a pterocarpanquinone with antitumor activity toward prostate Cancer cells. It inhibits cell proliferation by down-regulating cyclins D1 and B1 and up-regulating p21. However, the effects of LQB-118 on PCa cell migration are still unclear. Herein, the LQB-118 effects on PCa metastatic cell migration/invasion and its mechanism of action were evaluated.

Materials and methods: PC3 cells were treated with LQB-118 or Paclitaxel (PTX), and cell migration (wound healing and Boyden chamber assays) and invasion (matrigel assay) were determined. The LQB-118 mechanisms were evaluated by αVβIII protein expression (flow cytometry), protein phosphorylation (Western blot), and mRNA expression (qPCR).

Results: LQB-118 impaired PCa cell migration and invasion, down-regulated Akt phosphorylation, and also reduced GSK3β phosphorylation, through a FAK-independent pathway. Also, it was observed that LQB-118 controlled the invasiveness behavior by reducing matrix metalloproteinase-9 (MMP-9) and up-regulating reversion-inducing cysteine rich protein with Kazal motifs (Reck) mRNA levels. Interestingly, LQB-118 increased Integrin αvβIII expression, but this effect was not related to its activation, since the cell adhesion ability was reduced after LQB-118 treatment.

Conclusion: These data highlight novel LQB-118 mechanisms in prostate Cancer cells. LQB-118 acts as a negative regulator of the Akt/GSK3 signaling pathway and can modulate PCa cell proliferation, death, and migration/invasion. The results also support the use of LQB-118 for the treatment of metastatic PCa, alone or combined with another chemotherapeutic agent, due to its demonstrated pleiotropic activities.

Keywords
Akt; MMP-9; Pterocarpanquinone; prostate cancer.
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