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

Thiago Martino1, Graziele Freitas DE Bem2, Shirley Vania Moura Santos1

  • 1LIA-BPPN, Department of Biochemistry, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Anticancer Research
|December 30, 2022
PubMed
Abstract

Insights

LQB-118, a novel compound, inhibits prostate cancer (PCa) cell migration and invasion. It targets the Akt/GSK3 signaling pathway, offering potential for treating metastatic PCa.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Prostate cancer (PCa) is a prevalent malignancy in men.
  • LQB-118, a pterocarpanquinone, exhibits antitumor properties against PCa cells.
  • Previous studies showed LQB-118 inhibits proliferation; its effect on migration was unknown.

Purpose of the Study:

  • To evaluate the effects of LQB-118 on prostate cancer cell migration and invasion.
  • To elucidate the underlying mechanisms of LQB-118's action on PCa metastasis.

Main Methods:

  • PC3 cells were treated with LQB-118 or Paclitaxel.
  • Cell migration and invasion assays (wound healing, Boyden chamber, Matrigel) were performed.
  • Mechanisms were assessed via flow cytometry, Western blot, and qPCR for protein expression, phosphorylation, and mRNA levels.

Main Results:

  • LQB-118 significantly impaired PCa cell migration and invasion.
  • It down-regulated Akt and GSK3β phosphorylation via a FAK-independent pathway.
  • LQB-118 modulated MMP-9 and Reck mRNA levels, and affected integrin αvβIII expression without increasing cell adhesion.

Conclusions:

  • LQB-118 negatively regulates the Akt/GSK3 signaling pathway in prostate cancer cells.
  • It modulates PCa cell proliferation, death, and metastasis.
  • LQB-118 demonstrates pleiotropic activities, supporting its potential use in treating metastatic PCa.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.5K