PMID- 35660629
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20231213
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 54
DP  - 2022 Aug
TI  - Cationic antimicrobial peptide NRC-03 induces oral squamous cell carcinoma cell 
      apoptosis via CypD-mPTP axis-mediated mitochondrial oxidative stress.
PG  - 102355
LID - S2213-2317(22)00127-6 [pii]
LID - 10.1016/j.redox.2022.102355 [doi]
LID - 102355
AB  - Pleurocidin-family cationic antimicrobial peptide NRC-03 exhibits potent and 
      selective cytotoxicity towards cancer cells. However, the anticancer effect of 
      NRC-03 in oral squamous cell carcinoma (OSCC) and the molecular mechanism of 
      NRC-03 induced cancer cell death is still unclear. This study focused to 
      investigate mitochondrial oxidative stress-mediated altered mitochondrial 
      function involved in NRC-03-induced apoptosis of OSCC cells. NRC-03 entered the 
      OSCC cells more easily than that of normal cells and bound to mitochondria as 
      well as the nucleus, causing cell membrane blebbing, mitochondria swelling, and 
      DNA fragmentation. NRC-03 induced high oxygen consumption, reactive oxygen 
      species (ROS) release, mitochondrial dysfunction, and apoptosis in OSCC cells. 
      Non-specific antioxidant N-acetyl-l-cysteine (NAC), or mitochondria-specific 
      antioxidant mitoquinone (MitoQ) alleviated NRC-03-induced apoptosis and 
      mitochondrial dysfunction indicated that NRC-03 exerts a cytotoxic effect in 
      cancer cells via inducing cellular and mitochondrial oxidative stress. Moreover, 
      the expression of cyclophilin D (CypD), the key component of mitochondrial 
      permeability transition pore (mPTP), was upregulated in NRC-03-treated cancer 
      cells. Blockade of CypD by siRNA-mediated depletion or pharmacological inhibitor 
      cyclosporine A (CsA) significantly suppressed NRC-03-induced mitochondrial 
      oxidative stress, mitochondrial dysfunction, and apoptosis. NRC-03 also activated 
      MAPK/ERK and NF-kappaB pathways. Importantly, intratumoral administration of NRC-03 
      inhibited the growth of CAL-27 cells-derived tumors on xenografted animal models. 
      Taken together, our study indicates that NRC-03 induces apoptosis in OSCC cells 
      via the CypD-mPTP axis mediated mitochondrial oxidative stress.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Hou, Dan
AU  - Hou D
AD  - Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong 
      Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key 
      Laboratory of Basic and Applied Research of Oral Regenerative Medicine, 
      Guangzhou, Guangdong, 510182, China; Department of Oral and Maxillofacial 
      Surgery/Oral Pathology, Amsterdam UMC/VUmc and Academic Centre for Dentistry 
      Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, 
      Amsterdam, 1081 HZ, the Netherlands.
FAU - Hu, Fengjun
AU  - Hu F
AD  - Institute of Information Technology, Zhejiang Shuren University, Hangzhou, 
      Zhejiang, 310000, China.
FAU - Mao, Yixin
AU  - Mao Y
AD  - Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical 
      University, Wenzhou, 325027, China; Institute of Stomatology, School and Hospital 
      of Stomatology, Wenzhou Medical University, Wenzhou, 325027, China; Laboratory 
      for Myology, Department of Human Movement Sciences, Faculty of Behavioural and 
      Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 
      Amsterdam, 1081 HZ, Netherlands.
FAU - Yan, Liang
AU  - Yan L
AD  - Department of Medical Biochemistry and Molecular Biology, School of Medicine, 
      Jinan University, Guangzhou, 510632, China.
FAU - Zhang, Yuhui
AU  - Zhang Y
AD  - Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong 
      Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key 
      Laboratory of Basic and Applied Research of Oral Regenerative Medicine, 
      Guangzhou, Guangdong, 510182, China.
FAU - Zheng, Zhichao
AU  - Zheng Z
AD  - Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong 
      Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key 
      Laboratory of Basic and Applied Research of Oral Regenerative Medicine, 
      Guangzhou, Guangdong, 510182, China.
FAU - Wu, Antong
AU  - Wu A
AD  - Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong 
      Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key 
      Laboratory of Basic and Applied Research of Oral Regenerative Medicine, 
      Guangzhou, Guangdong, 510182, China.
FAU - Forouzanfar, Tymour
AU  - Forouzanfar T
AD  - Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam UMC/VUmc 
      and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, 
      Amsterdam Movement Science, Amsterdam, 1081 HZ, the Netherlands.
FAU - Pathak, Janak L
AU  - Pathak JL
AD  - Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong 
      Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key 
      Laboratory of Basic and Applied Research of Oral Regenerative Medicine, 
      Guangzhou, Guangdong, 510182, China. Electronic address: j.pathak@gzhmu.edu.cn.
FAU - Wu, Gang
AU  - Wu G
AD  - Department of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam UMC/VUmc 
      and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, 
      Amsterdam Movement Science, Amsterdam, 1081 HZ, the Netherlands; Department of 
      Oral Cell Biology, Academic Centre of Dentistry Amsterdam (ACTA), University van 
      Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, 1081LA, Netherlands. 
      Electronic address: g.wu@acta.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220528
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Antimicrobial Peptides)
RN  - 0 (Antioxidants)
RN  - 0 (Peptidyl-Prolyl Isomerase F)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
RN  - EC 5.2.1.- (Cyclophilins)
SB  - IM
MH  - Animals
MH  - Antimicrobial Cationic Peptides/pharmacology
MH  - Antimicrobial Peptides
MH  - Antioxidants/metabolism
MH  - Apoptosis
MH  - *Carcinoma, Squamous Cell/drug therapy
MH  - Peptidyl-Prolyl Isomerase F
MH  - Cyclophilins/metabolism
MH  - *Head and Neck Neoplasms
MH  - Mitochondrial Membrane Transport Proteins/metabolism
MH  - Mitochondrial Permeability Transition Pore
MH  - *Mouth Neoplasms/drug therapy
MH  - Oxidative Stress
MH  - Squamous Cell Carcinoma of Head and Neck
PMC - PMC9511698
OTO - NOTNLM
OT  - Cell apoptosis
OT  - Cyclophilin D
OT  - NRC-03
OT  - Oral squamous cell carcinoma
OT  - Oxidative stress
EDAT- 2022/06/07 06:00
MHDA- 2022/07/14 06:00
PMCR- 2022/05/28
CRDT- 2022/06/06 11:41
PHST- 2022/02/24 00:00 [received]
PHST- 2022/05/14 00:00 [revised]
PHST- 2022/05/24 00:00 [accepted]
PHST- 2022/06/07 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/06/06 11:41 [entrez]
PHST- 2022/05/28 00:00 [pmc-release]
AID - S2213-2317(22)00127-6 [pii]
AID - 102355 [pii]
AID - 10.1016/j.redox.2022.102355 [doi]
PST - ppublish
SO  - Redox Biol. 2022 Aug;54:102355. doi: 10.1016/j.redox.2022.102355. Epub 2022 May 
      28.