CO2 Plasma Activated Water (PAW), a Novel Weapon for Hepatocellular Carcinoma

Ujah, O. Frederick; Akpa, A. Maxwell; Abeda, T.  Isaac; Abana, N. Stanislas

doi:10.55006/biolsciences.2024.4209

Authors

Ujah, O. Frederick Department of Chemical Sciences, College of Science and Education, University of Mkar, Mkar, P.M.B. 017, Benue State, Nigeria https://orcid.org/0000-0002-5150-3703
Akpa, A. Maxwell Department of Chemical Sciences, College of Science and Education, University of Mkar, Mkar, P.M.B. 017, Benue State, Nigeria https://orcid.org/0009-0000-6998-4173
Abeda, T. Isaac Department of Chemical Sciences, College of Science and Education, University of Mkar, Mkar, P.M.B. 017, Benue State, Nigeria
Abana, N. Stanislas Department of Physical Sciences, College of Science and Education, University of Mkar, Mkar, P.M.B. 017, Benue State, Nigeria https://orcid.org/0000-0003-4582-1227

DOI:

https://doi.org/10.55006/biolsciences.2024.4209

Keywords:

CO2 Plasma Activated Water, Hepatocellular carcinoma, Cytotoxicity

Abstract

Cancer poses significant challenges to global health, necessitating the exploration of innovative therapies. CO2 plasma activated water (PAW) holds promise as a novel therapeutic agent due to its selective cytotoxicity against cancer cells while sparing healthy tissues. This study investigated the in-vitro cytotoxic activity of CO2 PAW against human hepatocarcinoma (HepG2) cells. The cytotoxic effect of CO2 PAW on HepG2 cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cells were seeded in 96-well plates, treated with varying volumes of PAW. Morphological changes induced by PAW treatment were assessed using phase-contrast microscopy. The total RNA isolated from HepG2 cells, treated with PAW using the GF-1 total RNA extraction kit, qRT-PCR was performed using SYBR-green master mix with cDNA templates and synthesized primers. Data were analyzed using GraphPad Prism (ver. 9.5, USA, 1992) and presented as mean ± standard error of means. The results revealed dose-dependent cytotoxic effects, with higher concentrations inducing pronounced cell death. Morphological changes in HepG2 cells post-PAW treatment and gene expression analysis showed significant (P<0.05) alterations in Bax and Bcl-2 mRNA levels, indicative of intrinsic apoptotic pathway activation.

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References

Song, Z., Wu, Y., Yang, J., Yang, D., Fang, X. Progress in the treatment of advanced gastric cancer. Tumor Biology, 2017, 39(7), 101.

Nguyen, P. L., Je, Y., Schutz, F. A., Hoffman, K. E., Hu, J. C., Parekh, A., Choueiri, T. K. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. Jama. 2011, 306(21), 2359-2366.

Abida, F., Saleema, M., Legharid, T., Rafid, I., Maqboole, T., Fatimad, F., Arshadd, A.M., Khurshidb, S., Nazf, S., Hadie, F., Tahire, M., Akhtare, S., Yasirh, S., Mobasharb A., Ashrafe M., Evaluation of in vitro anticancer potential of pharmacological ethanolic plant extracts Acacia modesta and Opuntiamonocantha against liver cancer cells, Brazilian Journal of Biology. 2021 (84):

Losic, B., Craig, A. J., Villacorta-Martin, C., Martins-Filho, S. N., Akers, N., Chen, X., Villanueva, A. Intratumoral heterogeneity and clonal evolution in liver cancer. Nature communications. 2020, 11(1), 291.

Mohammadian, M., Mahdavifar, N., Mohammadian-Hafshejani, A., Salehiniya, H. Liver cancer in the world: epidemiology, incidence, mortality and risk factors. World Cancer Research Journal, 2018, 5(2), e1082.

Dong, M., Pang, X., Xu, Y., Wen, F., Zhang, Y.. Ubiquitin-conjugating enzyme 9 promotes epithelial ovarian cancer cell proliferation in vitro. International journal of molecular science. 2013, 14(6), 11061-11071.

Park, J.H.; Park, J.S.; Lee, J.H.; Jeong, B.H. Space Sterilization Effect Through High-Density Plasma Ozone Using DBD Device. Journal of Electrical Engineering and Technology. 2022, 17, 2771–2778.

Zhang, Y.; Du, X.; Shi, Q.; Xiao,W.; Li, H. Precise Control of Glioma Cell Apoptosis Induced by Micro-Plasma-Activated Water (PAW). Micromachines 2022, 13, 2145.

Tanaka, H., Mizuno, M., Ishikawa, K., Toyokuni, S., Kajiyama, H., Kikkawa, F., Hori, M. New hopes for plasma-based cancer treatment. Plasma, 2018 1(1).

Mitra, S., Nguyen, L. N., Akter, M., Park, G., Choi, E. H., Kaushik, N. K. Impact of ROS Generated by Chemical, Physical, and Plasma Techniques on Cancer Attenuation. Cancers. 2019, 11(7), 1030.

Murillo, D., Huergo, C., Gallego, B., Rodríguez, R., Tornín, J. Exploring the Use of Cold Atmospheric Plasma to Overcome Drug Resistance in Cancer. Biomedicines, 2023, 11(1), 208

Chen Z, Chen G, Obenchain R, Zhang R, Bai F, Fang T, Wang H, Lu Y, Wirz RE, Gu Z. Cold atmospheric plasma delivery for biomedical applications. materials today. 2022 Apr 1;54:153-88.

Prior R. The Long Haul: How Long Covid Survivors Are Revolutionizing Health Care. MIT Press; 2024 Mar 5.

Upenieks L, Ellison CG. Changes in religiosity and reliance on god during the COVID-19 pandemic: A protective role under conditions of financial strain? Review of religious research, 2022 Dec; 64(4):853-81.

Mao JJ, Pillai GG, Andrade CJ, Ligibel JA, Basu P, Cohen L, Khan IA, Mustian KM, Puthiyedath R, Dhiman KS, Lao L. Integrative oncology: Addressing the global challenges of cancer prevention and treatment. CA: A Cancer Journal for Clinicians. 2022 Mar,72(2):144-64.

Dehelean CA, Marcovici I, Soica C, Mioc M, Coricovac D, Iurciuc S, Cretu OM, Pinzaru I. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules. 2021 Feb 19; 26(4):1109.

Subramanian, P. G., Jain, A., Shivapuji, A. M., Sundaresan, N. R., Dasappa, S., Rao, L. Plasma‐activated water from a dielectric barrier discharge plasma source for the selective treatment of cancer cells. Plasma Processes and Polymers, 2020, 17(8), 1900260.

Chen, T. P., Su, T. L., Liang, J. Plasma-activated solutions for bacteria and biofilm inactivation. Current Bioactive Compounds, 2017, 13(1), 59-65.

Veronico, V., Morelli, S., Piscioneri, A., Gristina, R., Casiello, M., Favia, P., Sardella, E. Anticancer Effects of Plasma-Treated Water Solutions from Clinically Approved Infusion Liquids Supplemented with Organic Molecules. ACS omega, 2023, 8(37), 33723-33736.

Ando, T., Suzuki-Karasaki, M., Suzuki-Karasaki, M., Ichikawa, J., Ochiai, T., Yoshida, Y., Suzuki-Karasaki. Synergistic anticancer effect of plasma-activated infusion and salinomycin by targeting autophagy and mitochondrial morphology. bioRxiv, 2020-10.

Mansoori, B., Mohammadi, A., Davudian, S., Shirjang, S., Baradaran, B. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Advanced pharmaceutical bulleti, 2017, 7(3), 339–348.

Raud S, Raud J, Jõgi I, Piller CT, Plank T, Talviste R, Teesalu T, Vasar E. The production of plasma activated water in controlled ambient gases and its impact on cancer cell viability. Plasma Chemistry and Plasma Processing. 2021 Sep; 41(5):1381-95.

Mahdikia, H., Shokri, B., Majidzadeh-A, K. The Feasibility Study of Plasma-activated Water as a Physical Therapy to Induce Apoptosis in Melanoma Cancer Cells In-vitro. Iranian journal of pharmaceutical research: International journal 0f production and research. 2021, 20(3), 337–350.

Bai, Y., Dai, C., Chen, N., Zhou, X., Li, H., Xu, Q., Xu, Y. Plasma-activated medium exerts tumor-specific inhib-itory effect on hepatocellular carcinoma via disruption of the salvage pathway. Journal of Clinical Biochemistry and Nutrition, 2024, 23-112.

Tanaka, H., Mizuno, M., Ishikawa, K., Nakamura, K., Kajiyama, H., Kano, H., Hori, M. Plasma-activated medium selectively kills glioblastoma brain tumor cells by down-regulating a survival signaling molecule, AKT kinase. Plasma Medicine, 2011, 1(3-4).

Yan, D., Sherman, J. H., Keidar, M. Cold atmospheric plasma, a novel promising anti-cancer treatment modality. Oncotarget, 2017, 8(9),

Li, Y., Tang, T., Lee, H. J., Song, K. Selective Anti-Cancer Effects of Plasma-Activated Medium and Its High Efficacy with Cisplatin on Hepatocellular Carcinoma with Cancer Stem Cell Characteristics. International journal of molecular sciences, 2021, 22(8), 3956.