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

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.

Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2

“…Moreover, other non-lytic pathogen-killing pathways, which involve the targeting of specific cellular factors, have also been reported [ 6 ]. Interestingly, some pathogen-killing activities may also allow AMPs to target cancer cells, and several AMPs have been implicated as promising anticancer agents for various cancers [ 7 , 8 , 9 , 10 , 11 , 12 ]. One such AMP, Tilapia piscidin (TP) 4, was identified in Nile tilapia ( Oreochromis niloticus ) [ 13 ].…”

“…One such AMP, Tilapia piscidin (TP) 4, was identified in Nile tilapia ( Oreochromis niloticus ) [ 13 ]. A growing body of literature has shown that a synthesized active segment of TP4 has broad-spectrum antibacterial activities [ 13 , 14 , 15 ] as well as excellent cancer cell-killing activity in different cancer types in vitro and in vivo [ 9 , 10 , 11 , 12 , 16 , 17 ]. Multiple anticancer mechanisms are thought to be involved in AMP-mediated cytotoxicity, including rapid cell membrane disruption at high-dose treatment [ 18 , 19 ].…”

TP3, an antimicrobial peptide, inhibits infiltration and motility of glioblastoma cells via modulating the tumor microenvironment

“…In addition, TP3 is important to the development of antibacterial drug research. To our best knowledge, there was no anti‐cancer research on TP3, while TP4 has been reported to have anti‐cancer activities 6,53 . The sequence between TP3 (FIHHIIGGLFSVGKHIHSLIHGH) and TP4 (FIHHIIGGLFSAGKAIHRLIRRRRR) is similar and both peptides have amphiphilic, α‐helical, cationic characteristics, suggesting that TP3 may have the potential to treat glioblastoma.…”

Nile Tilapia Derived Antimicrobial Peptide TP4 Exerts Antineoplastic Activity Through Microtubule Disruption

“…Many AMPs disrupt bacterial membranes via pore formation or a detergent-like action [8], while others operate via membrane non-lytic mechanisms [9]. Interestingly, a few synthesized AMPs have been shown to be cytotoxic to both antibiotic-resistant bacteria [4,5,6] and cancerous cell lines [10,11,12,13,14,15,16,17,18]. Cancer cells often harbor negatively charged plasma membranes, which attract cationic AMPs through electrostatic interactions [11,17,18].…”

“…The mechanisms underlying this anticancer activity have been reported to involve cellular uptake and the induction of mitochondrial and calcium homeostatic stresses, which trigger necrotic death [11]. Another report indicated that TP4 may induce apoptosis via activation of extrinsic Fas/FasL and intracellular intrinsic mitochondria-mediated pathways in osteosarcoma MG63 cells [10]. However, the intracellular targets of TP4 and the mechanisms leading to cell death remain largely uncharacterized.…”