Volume 10, Issue 4 (Vol.10 No.4 Jan 2022)                   rbmb.net 2022, 10(4): 640-652 | Back to browse issues page

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Zahedian S, Hekmat A, Hesami Tackallou S, Ghoranneviss M. The Impacts of Prepared Plasma-Activated Medium (PAM) Combined with Doxorubicin on the Viability of MCF-7 Breast Cancer Cells: A New Cancer Treatment Strategy. rbmb.net. 2022; 10 (4) :640-652
URL: http://rbmb.net/article-1-697-en.html
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Abstract:   (1050 Views)
Background: For many years, the chemotherapeutic agent doxorubicin (DOX) has been used to treat various cancers; however, DOX initiates several critical adverse effects. Many studies have reported that non-thermal atmospheric pressure plasma can provide novel, but challenging, treatment strategies for cancer patients. To date, tissues and cells have been treated with plasma-activated medium (PAM) as a practical therapy. Consequently, due to the harmful adverse effects of DOX, we were motivated to elucidate the impact of PAM in the presence of DOX on MCF-7 cell proliferation.

Methods: MTT assay, N-acetyl-L-cysteine (NAC) assay, and flow cytometry analysis were utilized in this research. 

Results: The results demonstrated that 0.45 μM DOX combined with 3-min PAM significantly induced apoptosis (p< 0.01) through intracellular ROS generation in MCF-7 when compared with 0.45 μM DOX alone or 3-min PAM alone. In contrast, after treatment with 0.45 μM DOX plus 4-min PAM, cell necrosis was increased. Hence, DOX combined with 4-min PAM has cytotoxic effects with different mechanisms than 4-min PAM alone, in which the number of apoptotic cells increases.

Conclusions: Although further investigations are crucial, low doses of DOX plus 3-min PAM could be a promising strategy for cancer therapy. The findings from this research may offer advantageous and innovative clinical strategies for cancer therapy using PAM.
Full-Text [PDF 2585 kb]   (606 Downloads)    
Type of Article: Original Article | Subject: Biochemistry
Received: 2021/05/1 | Accepted: 2021/07/26 | Published: 2022/02/7

1. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics 2020. CA Cancer J Clin. 2020;70:145-164. https://doi.org/10.3322/caac.21590 [DOI:10.3322/caac.21601]
2. Nourolahzadeh Z, Houshmand SM, Mostafa Mohammad F, Ghorbian S. Correlation between Lsp1 (Rs3817198) and Casc (Rs4784227) Polymorphisms and the Susceptibility to Breast Cancer. rbmb.net 2020;9:291-296. [DOI:10.29252/rbmb.9.3.291] [PMID] [PMCID]
3. Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321:288-300. [DOI:10.1001/jama.2018.19323] [PMID]
4. Jalili A, Irani S and Mirfakhraie R. Combination of cold atmospheric plasma and iron nanoparticles in breast cancer: Gene expression and apoptosis study. Onco Targets Ther. 2016;9:5911-5917. [DOI:10.2147/OTT.S95644] [PMID] [PMCID]
5. Lei J, Wang H, Zhu D, Wan Y, Yin L. Combined effects of avasimibe immunotherapy, doxorubicin chemotherapy, and metal-organic frameworks nanoparticles on breast cancer. Journal of Cellular Physiology. 2020;235(5):4814-4823. [DOI:10.1002/jcp.29358] [PMID]
6. Hekmat A, Saboury AA, Divsalar A, Seyedarabi A. Structural effects of TiO2 nanoparticles and doxorubicin on DNA and their antiproliferative roles in T47D and MCF7 cells. Anticancer Agents Med Chem. 2013;13:932-51. [DOI:10.2174/18715206113139990142] [PMID]
7. Lovitt CJ, Shelper TB, Avery VM. Doxorubicin resistance in breast cancer cells is mediated by extracellular matrix proteins. BMC Cancer. 2018;18(1):41. [DOI:10.1186/s12885-017-3953-6] [PMID] [PMCID]
8. Songbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicol Lett. 2019;307:41-48. [DOI:10.1016/j.toxlet.2019.02.013] [PMID]
9. Azzariti A, Iacobazzi RM, Di Fonte R, Porcelli L, Gristina R, Favia P, et al. Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells. Scientific Reports volume. 2019;9:1-13. [DOI:10.1038/s41598-019-40637-z] [PMID] [PMCID]
10. Gay-Mimbrera J, García MC, Isla-Tejera B, Rodero-Serrano A, García-Nieto AV, Ruano J. Clinical and biological principles of cold atmospheric plasma application in skin cancer. Adv Ther. 2016;33:894-909. [DOI:10.1007/s12325-016-0338-1] [PMID] [PMCID]
11. Karki SB, Gupta TT, Yildirim-Ayan E, Eisenmann KM, Ayan H. Investigation of non-thermal plasma effects on lung cancer cells within 3D collagen matrices. J Phys D. 2017;50:315401. [DOI:10.1088/1361-6463/aa7b10]
12. Yan D, Sherman JH, Keidar M. Cold atmospheric plasma, a novel promising anti-cancer treatment modality. Oncotarget. 2017;8:15977-15995. [DOI:10.18632/oncotarget.13304] [PMID] [PMCID]
13. Kajiyama H, Utsumi F, Nakamura K, Tanaka H, Toyokuni S, Hori M, et al. Future perspective of strategic non-thermal plasma therapy for cancer treatment. J Clin Biochem Nutr. 2017;60:33-38. [DOI:10.3164/jcbn.16-65] [PMID] [PMCID]
14. Stratmann B, Costea T-C, Nolte C, Hiller J, Schmidt J, Reindel J, et al. Effect of cold atmospheric plasma therapy vs standard therapy placebo on wound healing in patients with diabetic foot ulcers. JAMA Netw Open. 2020;3(7):e2010411. [DOI:10.1001/jamanetworkopen.2020.10411] [PMID] [PMCID]
15. Yamamoto K, Ohshima T, Kitano K, Ikawa S, Yamazaki H, Maeda N, Hosoya N. The efficacy of plasma-treated water as a root canal irrigant. Asian Pacific J Dent. 2017;17:23-30.
16. Raiser J, Zenker M. Argon plasma coagulation for open surgical and endoscopic applications: state of the art. Journal of Physics D: Applied Physics. 2006;39:3520. [DOI:10.1088/0022-3727/39/16/S10]
17. Adil BH, Al-Shammari AM, Murbat HH. Breast cancer treatment using cold atmospheric plasma generated by the FE-DBD scheme. Clinical Plasma Medicine. 2020;19:100103. [DOI:10.1016/j.cpme.2020.100103]
18. Nakamura K, Peng Y, Utsumi F, Tanaka H, Mizuno M, Toyokuni S, et al. Novel intraperitoneal treatment with non-thermal plasma-activated medium inhibits metastatic potential of ovarian cancer cells. Scientific Reports. 2017;7:6085. [DOI:10.1038/s41598-017-05620-6] [PMID] [PMCID]
19. Ishikawa K, Hosoi Y, Tanaka H, Jiang L, Toyokuni S, Nakamura K, et al. Non-thermal plasma-activated lactate solution kills U251SP glioblastoma cells in an innate reductive manner with altered metabolism. Arch Biochem Biophys. 2020;688:108414. [DOI:10.1016/j.abb.2020.108414] [PMID]
20. Tavares-da-Silva E, Pereira E, Pires AS, Neves AR, Braz-Guilherme C, Marques IA, et al. Cold Atmospheric Plasma, a Novel Approach against Bladder Cancer, with Higher Sensitivity for the High-Grade Cell Line. Biology (Basel). 2021;10(1):41. [DOI:10.3390/biology10010041] [PMID] [PMCID]
21. Yan D, Cui H, Zhu W, Nourmohammadi N, Milberg J, Zhang LG, et al. The specific vulnerabilities of cancer cells to the cold atmospheric plasma-stimulated solutions. Scientific reports. 2017;7:4479. [DOI:10.1038/s41598-017-04770-x] [PMID] [PMCID]
22. Adachi T, Tanaka H, Nonomura S, Hara H, Kondo S-I, Hori M. Plasma-activated medium induces A549 cell injury via a spiral apoptotic cascade involving the mitochondrial-nuclear network. Free Radic Biol Med. 2015;79:28-44. [DOI:10.1016/j.freeradbiomed.2014.11.014] [PMID]
23. Zhen X, Sun H-N, Liu R, Choi HS, Lee D-S. Non-thermal plasma-activated medium induces apoptosis of aspc1 cells through the ros-dependent autophagy pathway. In Vivo. 2020;34(1):143-153. [DOI:10.21873/invivo.11755] [PMID] [PMCID]
24. Shahmirani Z, Irani S, Atyabi SM, Mirpour S, Shadpour S, Ghorannevis. Effect of cold atmospheric pressure plasma and gold nanoparticles on cell viability. Annu Res Rev Biol. 2014:3108-18. [DOI:10.9734/ARRB/2014/7419]
25. Dashtaki A, Mahjoub S, Zabihi E, Pourbagher R. The Effects of Pre-Treatment and Post-Treatment of Thymol against tert-Butyl Hydroperoxide (t-BHP) Cytotoxicity in MCF-7 Cell Line and Fibroblast Derived Foreskin. Rep Biochem Mol Biol. 2020;9(3):338-347. [DOI:10.29252/rbmb.9.3.338] [PMID] [PMCID]
26. Ibrahim NE-S, Morsy H, Abdelgwad M. The Comparative Effect of Nisin and Thioridazine as Potential Anticancer Agents on Hepatocellular Carcinoma. Rep Biochem Mol Biol. 2021;9(4):452-462. [DOI:10.52547/rbmb.9.4.452] [PMID] [PMCID]
27. Rahman SNSA, Wahab NA, Abd Malek SN. In vitro morphological assessment of apoptosis induced by antiproliferative constituents from the rhizomes of Curcuma zedoaria. Evid Based Complement Alternat Med. 2013;2013:257108. [DOI:10.1155/2013/257108] [PMID] [PMCID]
28. Park S-B, Kim B, Bae H, Lee H, Lee S, Choi EH, et al. Differential epigenetic effects of atmospheric cold plasma on MCF-7 and MDA-MB-231 breast cancer cells. PLoS One. 2015;10(6):e0129931. [DOI:10.1371/journal.pone.0129931] [PMID] [PMCID]
29. Laroussi M. Effects of PAM on select normal and cancerous epithelial cells. Plasma Research Express. 2019;1(2):025010. [DOI:10.1088/2516-1067/ab1b8a]
30. Hattori N, Yamada S, Torii K, Takeda S, Nakamura K, Tanaka H, et al. Effectiveness of plasma treatment on pancreatic cancer cells. Int J Oncol. 2015;47(5):1655-1662. [DOI:10.3892/ijo.2015.3149] [PMID] [PMCID]
31. Keidar M, Walk R, Shashurin A, Srinivasan P, Sandler A, Dasgupta S, et al. Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy. Br J Cancer. 2011;105:1295-301. [DOI:10.1038/bjc.2011.386] [PMID] [PMCID]
32. Yoshikawa N, Liu W, Nakamura K, Yoshida K, Ikeda Y, Tanaka H, et al. Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway. Scientific Reports. 2020;10:1614. [DOI:10.1038/s41598-020-58667-3] [PMID] [PMCID]
33. Ikeda Ji, Tanaka H, Ishikawa K, Sakakita H, Ikehara Y, Hori M. Plasma‐activated medium (PAM) kills human cancer‐initiating cells. Pathol Int. 2018;68(1):23-30. [DOI:10.1111/pin.12617] [PMID]
34. Srdic-Rajic T, Santibañez JF, Kanjer K, Tisma-Miletic N, Cavic M, Galun D, et al. Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells. Scientific Reports. 2017;7:1-12. [DOI:10.1038/s41598-017-03898-0] [PMID] [PMCID]
35. Utsumi F, Kajiyama H, Nakamura K, Tanaka H, Hori M, Kikkawa F. Selective cytotoxicity of indirect nonequilibrium atmospheric pressure plasma against ovarian clear-cell carcinoma. SpringerPlus. 2014;3:398. [DOI:10.1186/2193-1801-3-398] [PMID] [PMCID]
36. 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. [DOI:10.1063/1.3694928]
37. Rasouli M, Mehdian H, Hajisharifi K, Amini E, Ostrikov K, Robert E. Plasma activated medium induces apoptosis in chemotherapy-resistant ovarian cancer cells: high selectivity and synergy with carboplatin. Plasma Process Polym. 2021;18:2100074. [DOI:10.1002/ppap.202100074]
38. 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. Journal of Physics D: Applied Physics. 2013;46:425401. [DOI:10.1088/0022-3727/46/42/425401]
39. Conway GE, Casey A, Milosavljevic V, Liu Y, Howe O, Cullen PJ, et al. Non-thermal atmospheric plasma induces ROS-independent cell death in U373MG glioma cells and augments the cytotoxicity of temozolomide. Br J Cancer. 2016;114:435-43. [DOI:10.1038/bjc.2016.12] [PMID] [PMCID]
40. Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, et al. ROS in cancer therapy: the bright side of the moon. Exp. Mol Med. 2020;52(2):192-203. [DOI:10.1038/s12276-020-0384-2] [PMID] [PMCID]
41. Hekmat A, Hatamie S, Bakhshi E. Probing the effects of synthesized silver nanowire/reduced graphene oxide composites on the structure and esterase-like activity of human serum albumin and its impacts on human endometrial stem cells: A new platform in nanomedicine. Nanomedicine Journal. 2021;8:42-56.
42. Hekmat A, Saboury AA. Structural Effects of the Synthetic cobalt-Manganese-Zinc Ferrite Nanoparticles (Co0.3Mn0.2Zn0.5Fe2O4 NPs) on DNA and its Antiproliferative Effect on T47D cells. BioNanoSci. 9, 821-832 (2019). [DOI:10.1007/s12668-019-00657-5]
43. Xiang L, Xu X, Zhang S, Cai D, Dai X. Cold atmospheric plasma conveys selectivity on triple negative breast cancer cells both in vitro and in vivo. Free Radic Biol Med. 2018;124:205-13. [DOI:10.1016/j.freeradbiomed.2018.06.001] [PMID]
44. Yan D, Talbot A, Nourmohammadi N, Cheng X, Canady J, Sherman J, et al. Principles of using cold atmospheric plasma stimulated media for cancer treatment. Scientific Reports. 2015;5:18339. [DOI:10.1038/srep18339] [PMID] [PMCID]
45. Saadati F, Mahdikia H, Abbaszadeh H-A, Abdollahifar M-A, Khoramgah MS, Shokri B. Comparison of direct and indirect cold atmospheric-pressure plasma methods in the B 16 F 10 melanoma cancer cells treatment. Sci Rep. 2018;8(1):7689. [DOI:10.1038/s41598-018-25990-9] [PMID] [PMCID]
46. Guerrero-Preston R, Ogawa T, Uemura M, Shumulinsky G, Valle BL, Pirini F, et al. Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells. Int J Mol Med. 2014;34:941-6. [DOI:10.3892/ijmm.2014.1849] [PMID] [PMCID]

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