TY - JOUR
T1 - Calcium-dependent calpain activation-mediated mitochondrial dysfunction and oxidative stress are required for cytotoxicity of epinecidin-1 in human synovial sarcoma SW982 cells
AU - Su, Bor Chyuan
AU - Li, Chao Chin
AU - Horng, Jiun Lin
AU - Chen, Jyh Yih
N1 - Funding Information:
This research was supported by intramural funding from the Marine Research Station (Jiaushi, Ilan), Institute of Cellular and Organismic Biology, Academia Sinica to Mr. Jyh-Yih Chen (Research Fellow). This work was financially supported by the iEGG and Animal Biotechnology Center from The Feature Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE-108-S-0023-A) in Taiwan.
Funding Information:
Funding: This research was supported by intramural funding from the Marine Research Station (Jiaushi, Ilan), Institute of Cellular and Organismic Biology, Academia Sinica to Mr. Jyh-Yih Chen (Research Fellow). This work was financially supported by the iEGG and Animal Biotechnology Center from The Feature Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE-108-S-0023-A) in Taiwan.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/3/2
Y1 - 2020/3/2
N2 - Synovial sarcoma is a rare but highly malignant and metastatic disease. Despite its relative sensitivity to chemotherapies, the high recurrence and low 5-year survival rate for this disease suggest that new effective therapeutic agents are urgently needed. Marine antimicrobial peptide epinecidin-1 (epi-1), which was identified from orange-spotted grouper (Epinephelus coioides), exhibits multiple biological effects, including bactericidal, immunomodulatory, and anticancer activities. However, the cytotoxic effects and mechanisms of epi-1 on human synovial sarcoma cells are still unclear. In this study, we report that epi-1 exhibits prominent antisynovial sarcoma activity in vitro and in a human SW982 synovial sarcoma xenograft model. Furthermore, we determined that calcium overload-induced calpain activation and subsequent oxidative stress and mitochondrial dysfunction are required for epi-1-mediated cytotoxicity. Interestingly, reactive oxygen species (ROS)-mediated activation of extracellular signal-regulated kinase (ERK) plays a protective role against epi-1-induced cytotoxicity. Our results provide insight into the molecular mechanisms underlying epi-1-induced cell death in human SW982 cells.
AB - Synovial sarcoma is a rare but highly malignant and metastatic disease. Despite its relative sensitivity to chemotherapies, the high recurrence and low 5-year survival rate for this disease suggest that new effective therapeutic agents are urgently needed. Marine antimicrobial peptide epinecidin-1 (epi-1), which was identified from orange-spotted grouper (Epinephelus coioides), exhibits multiple biological effects, including bactericidal, immunomodulatory, and anticancer activities. However, the cytotoxic effects and mechanisms of epi-1 on human synovial sarcoma cells are still unclear. In this study, we report that epi-1 exhibits prominent antisynovial sarcoma activity in vitro and in a human SW982 synovial sarcoma xenograft model. Furthermore, we determined that calcium overload-induced calpain activation and subsequent oxidative stress and mitochondrial dysfunction are required for epi-1-mediated cytotoxicity. Interestingly, reactive oxygen species (ROS)-mediated activation of extracellular signal-regulated kinase (ERK) plays a protective role against epi-1-induced cytotoxicity. Our results provide insight into the molecular mechanisms underlying epi-1-induced cell death in human SW982 cells.
KW - Calcium
KW - Calpain
KW - Epinecidin-1
KW - Mitochondrial dysfunction
KW - Oxidative stress
KW - Synovial sarcoma
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U2 - 10.3390/ijms21062109
DO - 10.3390/ijms21062109
M3 - Article
C2 - 32204400
AN - SCOPUS:85082249023
SN - 1661-6596
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
M1 - 2109
ER -