title: Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells.
abstract: Colorectal cancer is a common type of tumor among both men and women worldwide. Conventional remedies such as chemotherapies pose the risk of side‑effects, and in many cases cancer cells develop chemoresistance to these treatments. Non‑thermal gas plasma (NTGP) was recently identified as a potential tool for cancer treatment. In this study, we investigated the potential use of NTGP to control SNUC5 human colon carcinoma cells. We hypothesized that NTGP would generate reactive oxygen species (ROS) in these cells, resulting in induction of endoplasmic reticulum (ER) stress. ROS generation, expression of ER stress‑related proteins and mitochondrial calcium levels were analyzed. Our results confirmed that plasma‑generated ROS induce apoptosis in SNUC5 cells. Furthermore, we found that plasma exposure resulted in mitochondrial calcium accumulation and expression of unfolded protein response (UPR) proteins such as glucose‑related protein 78 (GRP78), protein kinase R (PKR)‑like ER kinase (PERK), and inositol‑requiring enzyme 1 (IRE1). Elevated expression of spliced X‑box binding protein 1 (XBP1) and CCAAT/enhancer‑binding protein homologous protein (CHOP) further confirmed that ROS generated by NTGP induces apoptosis through the ER stress signaling pathway.
authors: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors: Madduma Hewage Susara
authors: MH
authors: Ruwan Kumara
authors: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors: Mei Jing
authors: MJ
authors: Piao
authors: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors: Kyoung Ah
authors: KA
authors: Kang
authors: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors: Yea Seong
authors: YS
authors: Ryu
authors: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors: Jeong Eon
authors: JE
authors: Park
authors: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors: Kristina
authors: K
authors: Shilnikova
authors: Department of Chemical and Biological Engineering, Jeju National University, Jeju 63243, Republic of Korea.
authors: Jin Oh
authors: JO
authors: Jo
authors: Department of Chemical and Biological Engineering, Jeju National University, Jeju 63243, Republic of Korea.
authors: Young Sun
authors: YS
authors: Mok
authors: Department of Mechanical Engineering and Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea.
authors: Jennifer H
authors: JH
authors: Shin
authors: National Fusion Research Institute, Plasma Technology Research Center, Gunsan 54004, Republic of Korea.
authors: Yeonsoo
authors: Y
authors: Park
authors: National Fusion Research Institute, Plasma Technology Research Center, Gunsan 54004, Republic of Korea.
authors: Seong Bong
authors: SB
authors: Kim
authors: National Fusion Research Institute, Plasma Technology Research Center, Gunsan 54004, Republic of Korea.
authors: Suk Jae
authors: SJ
authors: Yoo
authors: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors: Jin Won
authors: JW
authors: Hyun
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002118:Calcium / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D058626:Plasma Gases / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000096:biosynthesis* / Q000235:genetics; D056811:Unfolded Protein Response / Q000235:genetics; D000071717:X-Box Binding Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D019892:eIF-2 Kinase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D058626:Plasma Gases; D017382:Reactive Oxygen Species; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D051742:Transcription Factor CHOP; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase; D002118:Calcium