Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells

Ruwan Kumara,Madduma Hewage Susara; Piao,Mei Jing; Kang,Kyoung Ah; Ryu,Yea Seong; Park,Jeong Eon; Shilnikova,Kristina; Jo,Jin Oh; Mok,Young Sun; Shin,Jennifer H.; Park,Yeonsoo; Kim,Seong Bong; Yoo,Suk Jae; Hyun,Jin Won

doi:10.3892/or.2016.5038

Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells

Authors:
- Madduma Hewage Susara Ruwan Kumara
- Mei Jing Piao
- Kyoung Ah Kang
- Yea Seong Ryu
- Jeong Eon Park
- Kristina Shilnikova
- Jin Oh Jo
- Young Sun Mok
- Jennifer H. Shin
- Yeonsoo Park
- Seong Bong Kim
- Suk Jae Yoo
- Jin Won Hyun
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Affiliations: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea, Department of Chemical and Biological Engineering, Jeju National University, Jeju 63243, Republic of Korea, Department of Mechanical Engineering and Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea, National Fusion Research Institute, Plasma Technology Research Center, Gunsan 54004, Republic of Korea
Published online on: August 24, 2016 https://doi.org/10.3892/or.2016.5038
Pages: 2268-2274

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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.

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