Skip to main content
Top
Published in: Gastric Cancer 3/2015

01-07-2015 | Original Article

Effectiveness of plasma treatment on gastric cancer cells

Authors: Koji Torii, Suguru Yamada, Kae Nakamura, Hiromasa Tanaka, Hiroaki Kajiyama, Kuniaki Tanahashi, Naoki Iwata, Mitsuro Kanda, Daisuke Kobayashi, Chie Tanaka, Tsutomu Fujii, Goro Nakayama, Masahiko Koike, Hiroyuki Sugimoto, Shuji Nomoto, Atsushi Natsume, Michitaka Fujiwara, Masaaki Mizuno, Masaru Hori, Hideyuki Saya, Yasuhiro Kodera

Published in: Gastric Cancer | Issue 3/2015

Login to get access

Abstract

Background

Treatment of peritoneal carcinomatosis arising from gastric cancer remains a considerable challenge. In recent years, the anticancer effect of nonequilibrium atmospheric pressure plasma (NEAPP) has been reported in several cancer cell lines. Use of NEAPP may develop into a new class of anticancer therapy that augments surgery, chemotherapy, and radiotherapy.

Method

Gastric cancer cells were assessed for changes in cell morphology and rate of proliferation after treatment with NEAPP-exposed medium (PAM). To explore the functional mechanism, caspase 3/7, annexin V, and uptake of reactive oxygen species (ROS) were evaluated, along with the effect of the ROS scavenger N-acetylcysteine (NAC).

Results

PAM treatment for 24 h affected cell morphology, suggestive of induction of apoptosis. PAM cytotoxicity was influenced by the time of exposure to PAM, the type of cell line, and the number of cells seeded. Cells treated with PAM for 2 h demonstrated activated caspase 3/7 and an increased proportion of annexin V-positive cells compared with untreated cells. Additionally, ROS uptake was observed in PAM-treated cells, whereas NAC reduced the cytotoxicity induced by PAM presumably through reduction of ROS uptake. Furthermore, CD44 variant 9, which reportedly leads to glutathione synthesis and suppresses stress signaling of ROS, was overexpressed in PAM-resistant cells.

Conclusions

PAM treatment induced apoptosis of gastric cancer cells through generation and uptake of ROS. Local administration of PAM could develop into an option to treat peritoneal carcinomatosis.
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef
2.
go back to reference Nakamura K, Ueyama T, Yao T, Xuan ZX, Ambe K, Adachi Y. Pathology and prognosis of gastric carcinoma. Findings in 10,000 patients who underwent primary gastrectomy. Cancer. 1992;70:1030–7.PubMedCrossRef Nakamura K, Ueyama T, Yao T, Xuan ZX, Ambe K, Adachi Y. Pathology and prognosis of gastric carcinoma. Findings in 10,000 patients who underwent primary gastrectomy. Cancer. 1992;70:1030–7.PubMedCrossRef
3.
go back to reference Yu CC, Levison DA, Dunn JA, Ward LC, Demonakou M, Allum WH, et al. Pathological prognostic factors in the second British Stomach Cancer Group trial of adjuvant therapy in resectable gastric cancer. Br J Cancer. 1995;71:1106–10.PubMedCentralPubMedCrossRef Yu CC, Levison DA, Dunn JA, Ward LC, Demonakou M, Allum WH, et al. Pathological prognostic factors in the second British Stomach Cancer Group trial of adjuvant therapy in resectable gastric cancer. Br J Cancer. 1995;71:1106–10.PubMedCentralPubMedCrossRef
4.
go back to reference Ishigami H, Kitayama J, Kaisaki S, Hidemura A, Kato M, Otani K, et al. Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis. Ann Oncol. 2010;21(1):67–70.PubMedCrossRef Ishigami H, Kitayama J, Kaisaki S, Hidemura A, Kato M, Otani K, et al. Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis. Ann Oncol. 2010;21(1):67–70.PubMedCrossRef
5.
6.
go back to reference Vandamme M, Robert E, Pesnel S, Barbosa E, Dozias S, Sobilo J, et al. Antitumor effect of plasma treatment on U87 glioma xenografts: preliminary results. Plasma Process Polym. 2010;7:264–73.CrossRef Vandamme M, Robert E, Pesnel S, Barbosa E, Dozias S, Sobilo J, et al. Antitumor effect of plasma treatment on U87 glioma xenografts: preliminary results. Plasma Process Polym. 2010;7:264–73.CrossRef
7.
go back to reference Yamazaki H, Ohshima T, Tsubota Y, Yamaguchi H, Jayawardena JA, Nishimura Y. Microbicidal activities of low frequency atmospheric pressure plasma jets on oral pathogens. Dent Mater J. 2011;30:384–91.PubMedCrossRef Yamazaki H, Ohshima T, Tsubota Y, Yamaguchi H, Jayawardena JA, Nishimura Y. Microbicidal activities of low frequency atmospheric pressure plasma jets on oral pathogens. Dent Mater J. 2011;30:384–91.PubMedCrossRef
8.
go back to reference Fridman G, Friedman G, Gutsol A, Shekhter AB, Vasilets VN, Fridman A. Applied plasma medicine. Plasma Process Polym. 2008;5:503–33.CrossRef Fridman G, Friedman G, Gutsol A, Shekhter AB, Vasilets VN, Fridman A. Applied plasma medicine. Plasma Process Polym. 2008;5:503–33.CrossRef
9.
go back to reference Morfill GE, Kong MG, Zimmermann JL. Focus on plasma medicine. New J Phys. 2009;11(11):115011.CrossRef Morfill GE, Kong MG, Zimmermann JL. Focus on plasma medicine. New J Phys. 2009;11(11):115011.CrossRef
10.
go back to reference Yousfi M, Merbahi N, Pathak A, Eichwald O. Low-temperature plasmas at atmospheric pressure: toward new pharmaceutical treatments in medicine. Fundam Clin Pharmacol. 2013. doi:10.1111/fcp.12018.PubMed Yousfi M, Merbahi N, Pathak A, Eichwald O. Low-temperature plasmas at atmospheric pressure: toward new pharmaceutical treatments in medicine. Fundam Clin Pharmacol. 2013. doi:10.​1111/​fcp.​12018.PubMed
11.
go back to reference Brun P, Brun P, Vono M, Venier P, Tarricone E, Deligianni V, et al. Disinfection of ocular cells and tissues by atmospheric-pressure cold plasma. PLoS ONE. 2012;7(3):e33245.PubMedCentralPubMedCrossRef Brun P, Brun P, Vono M, Venier P, Tarricone E, Deligianni V, et al. Disinfection of ocular cells and tissues by atmospheric-pressure cold plasma. PLoS ONE. 2012;7(3):e33245.PubMedCentralPubMedCrossRef
12.
go back to reference Fridman G, Peddinghaus M, Balasubramanian M, Ayan H, Fridman A, Gutsol A, et al. Blood coagulation and living tissue sterilization by floating-electrode dielectric barrier discharge in air. Plasma Chem Plasma Process. 2006;26:425–42.CrossRef Fridman G, Peddinghaus M, Balasubramanian M, Ayan H, Fridman A, Gutsol A, et al. Blood coagulation and living tissue sterilization by floating-electrode dielectric barrier discharge in air. Plasma Chem Plasma Process. 2006;26:425–42.CrossRef
13.
go back to reference Lee JK, Kim, Byun JH, Kim KT, Kim GC, Park GY. Biochemical applications of low temperature atmospheric pressure plasmas to cancerous cell treatment and tooth breaching. Jpn J Appl Phys. 2011;50:08JF01.CrossRef Lee JK, Kim, Byun JH, Kim KT, Kim GC, Park GY. Biochemical applications of low temperature atmospheric pressure plasmas to cancerous cell treatment and tooth breaching. Jpn J Appl Phys. 2011;50:08JF01.CrossRef
14.
go back to reference Sato T, Yokoyama M, Johkura K. A key inactivation factor of HeLa cell viability by a plasma flow. J Phys D Appl Phys. 2011;44(37):372001.CrossRef Sato T, Yokoyama M, Johkura K. A key inactivation factor of HeLa cell viability by a plasma flow. J Phys D Appl Phys. 2011;44(37):372001.CrossRef
15.
go back to reference Sensenig R, Kalghatgi S, Cerchar E, Fridman G, Shereshevsky A, Torabi B, et al. Non-thermal plasma induces apoptosis in melanoma cells via production of intracellular reactive oxygen species. Ann Biomed Eng. 2011;39:674–87. Retraction in: Ann Biomed Eng. 2013;41(3):656.PubMedCentralPubMedCrossRef Sensenig R, Kalghatgi S, Cerchar E, Fridman G, Shereshevsky A, Torabi B, et al. Non-thermal plasma induces apoptosis in melanoma cells via production of intracellular reactive oxygen species. Ann Biomed Eng. 2011;39:674–87. Retraction in: Ann Biomed Eng. 2013;41(3):656.PubMedCentralPubMedCrossRef
16.
go back to reference Utsumi F, Kajiyama H, Nakamura K, Tanaka H, Mizuno M, Ishikawa K, et al. Effect of indirect nonequilibrium atmospheric pressure plasma on anti-proliferative activity against chronic chemo-resistant ovarian cancer cells in vitro and in vivo. PLoS ONE. 2013;8(12):e81576.PubMedCentralPubMedCrossRef Utsumi F, Kajiyama H, Nakamura K, Tanaka H, Mizuno M, Ishikawa K, et al. Effect of indirect nonequilibrium atmospheric pressure plasma on anti-proliferative activity against chronic chemo-resistant ovarian cancer cells in vitro and in vivo. PLoS ONE. 2013;8(12):e81576.PubMedCentralPubMedCrossRef
17.
go back to reference Iseki S, Nakamura K, Hayashi M, Tanaka H, Kondo H, Kajiyama H, et al. Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma. Appl Phys Lett. 2012;100(11):113702.CrossRef Iseki S, Nakamura K, Hayashi M, Tanaka H, Kondo H, Kajiyama H, et al. Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma. Appl Phys Lett. 2012;100(11):113702.CrossRef
18.
go back to reference Ito T, Yamada S, Tanaka C, Ito S, Murai T, Kobayashi D, et al. Overexpression of L1CAM is associated with tumor progression and prognosis via ERK signaling in gastric cancer. Ann Surg Oncol. 2014;21(2):560–8.PubMedCrossRef Ito T, Yamada S, Tanaka C, Ito S, Murai T, Kobayashi D, et al. Overexpression of L1CAM is associated with tumor progression and prognosis via ERK signaling in gastric cancer. Ann Surg Oncol. 2014;21(2):560–8.PubMedCrossRef
19.
go back to reference Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc− and thereby promotes tumor growth. Cancer Cell. 2011;19:387–400.PubMedCrossRef Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc and thereby promotes tumor growth. Cancer Cell. 2011;19:387–400.PubMedCrossRef
20.
go back to reference Kim CH, Kwon S, Bahn JH, Lee K, Jun SI, Rack PD, et al. Effects of atmospheric nonthermal plasma on invasion of colorectal cancer cells. Appl Phys Lett. 2010;96(24):243701.PubMedCentralPubMedCrossRef Kim CH, Kwon S, Bahn JH, Lee K, Jun SI, Rack PD, et al. Effects of atmospheric nonthermal plasma on invasion of colorectal cancer cells. Appl Phys Lett. 2010;96(24):243701.PubMedCentralPubMedCrossRef
21.
go back to reference Fridman G, Shereshevsky A, Jost M, Brooks A, Fridman A, Gutsol A, et al. Floating electrode dielectric barrier discharge plasma in air promoting apoptotic behavior in melanoma skin cancer cell lines. Plasma Chem Plasma Process. 2007;27:163–76.CrossRef Fridman G, Shereshevsky A, Jost M, Brooks A, Fridman A, Gutsol A, et al. Floating electrode dielectric barrier discharge plasma in air promoting apoptotic behavior in melanoma skin cancer cell lines. Plasma Chem Plasma Process. 2007;27:163–76.CrossRef
22.
go back to reference Tanaka H, Mizuno M, Ishikawa K, Nakamura K, Kajiyama H, Kano H, et al. Plasma-activated medium selectively kills glioblastoma brain tumor cells by down-regulating a survival signaling molecule, AKT kinase. Plasma Med. 2011;1(3–4):265–77.CrossRef Tanaka H, Mizuno M, Ishikawa K, Nakamura K, Kajiyama H, Kano H, et al. Plasma-activated medium selectively kills glioblastoma brain tumor cells by down-regulating a survival signaling molecule, AKT kinase. Plasma Med. 2011;1(3–4):265–77.CrossRef
23.
go back to reference Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43.PubMedCrossRef Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43.PubMedCrossRef
24.
go back to reference Heiss MM, Murawa P, Koralewski P, Kutarsa E, Kolesnik OO, Ivanchenko VV, et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer. 2010;127:2209–21.PubMedCentralPubMedCrossRef Heiss MM, Murawa P, Koralewski P, Kutarsa E, Kolesnik OO, Ivanchenko VV, et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer. 2010;127:2209–21.PubMedCentralPubMedCrossRef
25.
go back to reference Ma R, Feng H, Li F, Liang Y, Zhang Q, Zhu W, et al. An evaluation of anti-oxidative protection for cells against atmospheric pressure cold plasma treatment. Appl Phys Lett. 2012;100(12):123701.CrossRef Ma R, Feng H, Li F, Liang Y, Zhang Q, Zhu W, et al. An evaluation of anti-oxidative protection for cells against atmospheric pressure cold plasma treatment. Appl Phys Lett. 2012;100(12):123701.CrossRef
26.
go back to reference Ninomiya K, Ishijima T, Imamura M, Yamahara T, Enomoto H, Takahashi K, et al. Evaluation of extra- and intracellular OH radical generation, cancer cell injury, and apoptosis induced by a non-thermal atmospheric-pressure plasma jet. J Phys D Appl Phys. 2013;46(42):425401.CrossRef Ninomiya K, Ishijima T, Imamura M, Yamahara T, Enomoto H, Takahashi K, et al. Evaluation of extra- and intracellular OH radical generation, cancer cell injury, and apoptosis induced by a non-thermal atmospheric-pressure plasma jet. J Phys D Appl Phys. 2013;46(42):425401.CrossRef
27.
go back to reference Chan SW, Nguyen PN, Ayele D, Chevalier S, Aprikian A, Chen JZ. Mitochondrial DNA damage is sensitive to exogenous H2O2 but independent of cellular ROS production in prostate cancer cells. Mutat Res. 2011;716(1–2):40–50.PubMedCrossRef Chan SW, Nguyen PN, Ayele D, Chevalier S, Aprikian A, Chen JZ. Mitochondrial DNA damage is sensitive to exogenous H2O2 but independent of cellular ROS production in prostate cancer cells. Mutat Res. 2011;716(1–2):40–50.PubMedCrossRef
28.
29.
go back to reference Liu J, Ma L, Xu J, Liu C, Zhang J, Liu J, et al. Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties. Int J Oncol. 2013;42(2):453–9.PubMedCentralPubMed Liu J, Ma L, Xu J, Liu C, Zhang J, Liu J, et al. Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties. Int J Oncol. 2013;42(2):453–9.PubMedCentralPubMed
30.
go back to reference Mayer B, Jauch KW, Gunthert U, Figdor CG, Schildberg FW, Funke I, et al. De novo expression of CD44 and survival in gastric cancer. Lancet. 1993;342(8878):1019–22.PubMedCrossRef Mayer B, Jauch KW, Gunthert U, Figdor CG, Schildberg FW, Funke I, et al. De novo expression of CD44 and survival in gastric cancer. Lancet. 1993;342(8878):1019–22.PubMedCrossRef
31.
go back to reference Shibuya Y, Okabayashi T, Oda K, Tanaka N. Ratio of CD44 epithelial variant to CD44 hematopoietic variant is a useful prognostic indicator in gastric and colorectal carcinoma. Jpn J Clin Oncol. 1998;28(10):609–14.PubMedCrossRef Shibuya Y, Okabayashi T, Oda K, Tanaka N. Ratio of CD44 epithelial variant to CD44 hematopoietic variant is a useful prognostic indicator in gastric and colorectal carcinoma. Jpn J Clin Oncol. 1998;28(10):609–14.PubMedCrossRef
32.
go back to reference Györffy B, Schäfer R. Biomarkers downstream of RAS: a search for robust transcriptional targets. Curr Cancer Drug Targets. 2010;10:858–68.PubMedCrossRef Györffy B, Schäfer R. Biomarkers downstream of RAS: a search for robust transcriptional targets. Curr Cancer Drug Targets. 2010;10:858–68.PubMedCrossRef
33.
go back to reference Yoshida GJ, Saya H. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation. Biochem Biophys Res Commun. 2014;443(2):622–7.PubMedCrossRef Yoshida GJ, Saya H. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation. Biochem Biophys Res Commun. 2014;443(2):622–7.PubMedCrossRef
34.
go back to reference Nicco C, Laurent A, Chereau C, Weill B, Batteux F. Differential modulation of normal and tumor cell proliferation by reactive oxygen species. Biomed Pharmacother. 2005;59(4):169–74.PubMedCrossRef Nicco C, Laurent A, Chereau C, Weill B, Batteux F. Differential modulation of normal and tumor cell proliferation by reactive oxygen species. Biomed Pharmacother. 2005;59(4):169–74.PubMedCrossRef
Metadata
Title
Effectiveness of plasma treatment on gastric cancer cells
Authors
Koji Torii
Suguru Yamada
Kae Nakamura
Hiromasa Tanaka
Hiroaki Kajiyama
Kuniaki Tanahashi
Naoki Iwata
Mitsuro Kanda
Daisuke Kobayashi
Chie Tanaka
Tsutomu Fujii
Goro Nakayama
Masahiko Koike
Hiroyuki Sugimoto
Shuji Nomoto
Atsushi Natsume
Michitaka Fujiwara
Masaaki Mizuno
Masaru Hori
Hideyuki Saya
Yasuhiro Kodera
Publication date
01-07-2015
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 3/2015
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-014-0395-6

Other articles of this Issue 3/2015

Gastric Cancer 3/2015 Go to the issue