Piscidin-1 Induces Apoptosis via Mitochondrial Reactive Oxygen Species-Regulated Mitochondrial Dysfunction in Human Osteosarcoma Cells

Meng-Hsuan Cheng,Jin-Wei Wang,Nan-Fu Chen,Wen-Hsien Lu,Hsiao-Mei Kuo,San-Nan Yang,Chieh-Yu Pan,Wu-Fu Chen,Zhi-Hong Wen,Shuchen Hsieh

doi:10.1038/s41598-020-61876-5

Abstract

Osteosarcoma (OSA) is the most common type of cancer that originates in the bone and usually occurs in young children. OSA patients were treated with neoadjuvant chemotherapy and surgery, and the results were disappointing. Marine antimicrobial peptides (AMPs) have been the focus of antibiotic research because they are resistant to pathogen infection. Piscidin-1 is an AMP from the hybrid striped bass (Morone saxatilis × M. chrysops) and has approximately 22 amino acids. Research has shown that piscidin-1 can inhibit bacterial infections and has antinociception and anti-cancer properties; however, the regulatory effects of piscidin-1 on mitochondrial dysfunction in cancer cells are still unknown. We aimed to identify the effects of piscidin-1 on mitochondrial reactive oxygen species (mtROS) and apoptosis in OSA cells. Our analyses indicated that piscidin-1 has more cytotoxic effects against OSA cells than against lung and ovarian cancer cells; however, it has no effect on non-cancer cells. Piscidin-1 induces apoptosis in OSA cells, regulates mtROS, reduces mitochondrial antioxidant manganese superoxide dismutase and mitochondrial transmembrane potential, and decreases adenosine 5′-triphosphate production, thus leading to mitochondrial dysfunction and apoptosis. The mitochondrial antioxidant, mitoTempo, reduces the apoptosis induced by piscidin-1. Results suggest that piscidin-1 has potential for use in OSA treatment.

Highlights

IntroductionIt produces an apoptosis phenomenon, which is sometimes called programmed cell death[8]
When cells commit suicide, it produces an apoptosis phenomenon, which is sometimes called programmed cell death[8]
We first determined the cytotoxicity of treatment with piscidin-1 for 24 h on various cancer and noncancer cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide (MTT) staining, and the results showed that the effects of the treatment were dose-dependent

Summary

Introduction

It produces an apoptosis phenomenon, which is sometimes called programmed cell death[8]. Recent studies have shown that high concentrations of ROS, as produced from exposure to many chemotherapeutic drugs, can generate a cytotoxic effect and induce apoptosis of cancer cells via disruption of the mitochondrial membrane and function[15,16]. Based on cellular process involvement, mitochondrial dynamic imbalance may be responsible for the mitochondrial dysfunction of many diseases In this situation, the unbalance between mitochondrial fission and fusion, as caused by oxidative stress, affects the metabolism and function of the mitochondria, and may be related to the occurrence and development of various human diseases, including neurodegenerative diseases, cardiac metabolic diseases, and cancer[21]. This study aims to investigate the inhibitory abilities of piscidin-1 on various cancer cells, as well as apoptosis-induced by mitochondrial oxidative stress and oxidative phosphorylation

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Conclusion