Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells
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...
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| Veröffentlicht in: | Oncology reports 2016-10, Vol.36 (4), p.2268-2274 |
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| creator | Susara Ruwan Kumara, Madduma Hewage 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 |
| description | 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. |
| doi_str_mv | 10.3892/or.2016.5038 |
| format | Article |
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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.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2016.5038</identifier><identifier>PMID: 27573888</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Apoptosis ; Apoptosis - genetics ; Apoptosis - radiation effects ; Calcium - metabolism ; Cancer therapies ; Care and treatment ; CCAAT/enhancer-binding protein homologous protein ; Cell culture ; Cellular signal transduction ; Charged particles ; Colonic Neoplasms - genetics ; Colonic Neoplasms - pathology ; Colonic Neoplasms - therapy ; Colorectal cancer ; eIF-2 Kinase - biosynthesis ; eIF-2 Kinase - genetics ; Endoplasmic reticulum ; endoplasmic reticulum stress ; Endoplasmic Reticulum Stress - genetics ; Endoplasmic Reticulum Stress - radiation effects ; Flow cytometry ; Gene Expression Regulation, Neoplastic - radiation effects ; Health aspects ; Heat-Shock Proteins - biosynthesis ; Heat-Shock Proteins - genetics ; High temperature plasmas ; Homeostasis ; Humans ; Mitochondria ; Mitochondria - metabolism ; non-thermal gas plasma ; Oxidative stress ; Plasma ; Plasma (Ionized gases) ; Plasma Gases - therapeutic use ; Protein folding ; Protein synthesis ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Transcription Factor CHOP - biosynthesis ; Transcription Factor CHOP - genetics ; unfolded protein response ; Unfolded Protein Response - genetics ; X-Box Binding Protein 1 - biosynthesis ; X-Box Binding Protein 1 - genetics</subject><ispartof>Oncology reports, 2016-10, Vol.36 (4), p.2268-2274</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-839d189e9ec5f6b1addeedcd3a4234d168597b7b225c50de619c8fe0b0e4d1003</citedby><cites>FETCH-LOGICAL-c552t-839d189e9ec5f6b1addeedcd3a4234d168597b7b225c50de619c8fe0b0e4d1003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27573888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Susara Ruwan Kumara, Madduma Hewage</creatorcontrib><creatorcontrib>Piao, Mei Jing</creatorcontrib><creatorcontrib>Kang, Kyoung Ah</creatorcontrib><creatorcontrib>Ryu, Yea Seong</creatorcontrib><creatorcontrib>Park, Jeong Eon</creatorcontrib><creatorcontrib>Shilnikova, Kristina</creatorcontrib><creatorcontrib>Jo, Jin Oh</creatorcontrib><creatorcontrib>Mok, Young Sun</creatorcontrib><creatorcontrib>Shin, Jennifer H</creatorcontrib><creatorcontrib>Park, Yeonsoo</creatorcontrib><creatorcontrib>Kim, Seong Bong</creatorcontrib><creatorcontrib>Yoo, Suk Jae</creatorcontrib><creatorcontrib>Hyun, Jin Won</creatorcontrib><title>Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>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.</description><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis - radiation effects</subject><subject>Calcium - metabolism</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>CCAAT/enhancer-binding protein homologous protein</subject><subject>Cell culture</subject><subject>Cellular signal transduction</subject><subject>Charged particles</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colonic Neoplasms - therapy</subject><subject>Colorectal cancer</subject><subject>eIF-2 Kinase - biosynthesis</subject><subject>eIF-2 Kinase - genetics</subject><subject>Endoplasmic reticulum</subject><subject>endoplasmic reticulum stress</subject><subject>Endoplasmic Reticulum Stress - genetics</subject><subject>Endoplasmic Reticulum Stress - radiation effects</subject><subject>Flow cytometry</subject><subject>Gene Expression Regulation, Neoplastic - radiation effects</subject><subject>Health aspects</subject><subject>Heat-Shock Proteins - biosynthesis</subject><subject>Heat-Shock Proteins - genetics</subject><subject>High temperature plasmas</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>non-thermal gas plasma</subject><subject>Oxidative stress</subject><subject>Plasma</subject><subject>Plasma (Ionized gases)</subject><subject>Plasma Gases - therapeutic use</subject><subject>Protein folding</subject><subject>Protein synthesis</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Transcription Factor CHOP - biosynthesis</subject><subject>Transcription Factor CHOP - genetics</subject><subject>unfolded protein response</subject><subject>Unfolded Protein Response - genetics</subject><subject>X-Box Binding Protein 1 - biosynthesis</subject><subject>X-Box Binding Protein 1 - genetics</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkk1rFTEUhgdRbK3uXEtAEBfONR-TTGZZil9QdKPgLuQmZ3pzySRjzszCf2_G1taKBJJw8pw3Jzlv0zxndCf0wN_msuOUqZ2kQj9oTlk_sJZ3gj2se8pZK4T8ftI8QTxSynuqhsfNCe9lL7TWp83xc07tcoAy2UiuLJI5WpxsG5JfHXgCyeffoeBIgSW4Na4TwaUAIpnAB7sAEjvneckYkIREDutkE3E55jrb5KAQBzHi0-bRaCPCs5v1rPn2_t3Xi4_t5ZcPny7OL1snJV9aLQbP9AADODmqPbPeA3jnhe246DxTWg79vt9zLp2kHhQbnB6B7inUU0rFWfP6Wncu-ccKuJgp4FaBTZBXNExzWiV6pir68h_0mNeSanWGDYKrXnAq7qgrG8GENOalWLeJmvNOKd0pqbpK7f5D1eGhfl5OMIYav5fw6q-EA9i4HDDHdQk54X3wzTXoSkYsMJq5hMmWn4ZRs3nA5GI2D5jNAxV_cfOodV87dAv_afrdxTjb5IPPeMvk0grV0q7lXGnxC3CxuCI</recordid><startdate>20161001</startdate><enddate>20161001</enddate><creator>Susara Ruwan Kumara, Madduma Hewage</creator><creator>Piao, Mei Jing</creator><creator>Kang, Kyoung Ah</creator><creator>Ryu, Yea Seong</creator><creator>Park, Jeong Eon</creator><creator>Shilnikova, Kristina</creator><creator>Jo, Jin Oh</creator><creator>Mok, Young Sun</creator><creator>Shin, Jennifer H</creator><creator>Park, Yeonsoo</creator><creator>Kim, Seong Bong</creator><creator>Yoo, Suk Jae</creator><creator>Hyun, Jin Won</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20161001</creationdate><title>Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells</title><author>Susara Ruwan Kumara, Madduma Hewage ; 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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-839d189e9ec5f6b1addeedcd3a4234d168597b7b225c50de619c8fe0b0e4d1003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Apoptosis</topic><topic>Apoptosis - 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Academic</collection><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Susara Ruwan Kumara, Madduma Hewage</au><au>Piao, Mei Jing</au><au>Kang, Kyoung Ah</au><au>Ryu, Yea Seong</au><au>Park, Jeong Eon</au><au>Shilnikova, Kristina</au><au>Jo, Jin Oh</au><au>Mok, Young Sun</au><au>Shin, Jennifer H</au><au>Park, Yeonsoo</au><au>Kim, Seong Bong</au><au>Yoo, Suk Jae</au><au>Hyun, Jin Won</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2016-10-01</date><risdate>2016</risdate><volume>36</volume><issue>4</issue><spage>2268</spage><epage>2274</epage><pages>2268-2274</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><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.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>27573888</pmid><doi>10.3892/or.2016.5038</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Apoptosis Apoptosis - genetics Apoptosis - radiation effects Calcium - metabolism Cancer therapies Care and treatment CCAAT/enhancer-binding protein homologous protein Cell culture Cellular signal transduction Charged particles Colonic Neoplasms - genetics Colonic Neoplasms - pathology Colonic Neoplasms - therapy Colorectal cancer eIF-2 Kinase - biosynthesis eIF-2 Kinase - genetics Endoplasmic reticulum endoplasmic reticulum stress Endoplasmic Reticulum Stress - genetics Endoplasmic Reticulum Stress - radiation effects Flow cytometry Gene Expression Regulation, Neoplastic - radiation effects Health aspects Heat-Shock Proteins - biosynthesis Heat-Shock Proteins - genetics High temperature plasmas Homeostasis Humans Mitochondria Mitochondria - metabolism non-thermal gas plasma Oxidative stress Plasma Plasma (Ionized gases) Plasma Gases - therapeutic use Protein folding Protein synthesis Reactive oxygen species Reactive Oxygen Species - metabolism Transcription Factor CHOP - biosynthesis Transcription Factor CHOP - genetics unfolded protein response Unfolded Protein Response - genetics X-Box Binding Protein 1 - biosynthesis X-Box Binding Protein 1 - genetics |
| title | Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells |
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