MSP-4, an Antimicrobial Peptide, Induces Apoptosis via Activation of Extrinsic Fas/FasL- and Intrinsic Mitochondria-Mediated Pathways in One Osteosarcoma Cell Line

Mar Drugs. 2018 Jan 2;16(1):8. doi: 10.3390/md16010008.

Abstract

Osteosarcoma (OS) is a common malignant bone cancer. The relatively high density of a person's bone structure means low permeability for drugs, and so finding drugs that can be more effective is important and should not be delayed. MSPs are marine antimicrobial peptides (AMP) and natural compounds extracted from Nile tilapia (Oreochromis niloticus). MSP-4 is a part of the AMPs series, with the advantage of having a molecular weight of about 2.7-kDa and anticancer effects, although the responsible anticancer mechanism is not very clear. The goal of this study is to determine the workings of the mechanism associated with apoptosis resulting from MSP-4 in osteosarcoma MG63 cells. The study showed that MSP-4 significantly induced apoptosis in MG63 cells, with Western blot indicating that MSP-4 induced this apoptosis through an intrinsic pathway and an extrinsic pathway. Thus, a pretreatment system with a particular inhibitor of Z-IETD-FMK (caspase-8 inhibitor) and Z-LEHD-FMK (caspase-9 inhibitor) significantly attenuated the cleavage of caspase-3 and prevented apoptosis. These observations indicate that low concentrations of MSP-4 can help induce the apoptosis of MG63 through a Fas/FasL- and mitochondria-mediated pathway and suggest a potentially innovative alternative to the treatment of human osteosarcoma.

Keywords: Fas/FasL pathway; antimicrobial peptide; apoptosis; mitochondria pathways; osteosarcoma.

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / isolation & purification
  • Anti-Infective Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Blotting, Western
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Caspase 8 / drug effects
  • Caspase 8 / metabolism
  • Caspase 9 / drug effects
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cichlids / metabolism*
  • Fas Ligand Protein / metabolism
  • Humans
  • Mitochondria / drug effects
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Peptides / chemistry
  • Peptides / isolation & purification
  • Peptides / pharmacology
  • fas Receptor / metabolism

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Peptides
  • fas Receptor
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9