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Cold atmospheric plasma (CAP) is considered to be a very promising cancer treatment method due to its “selective” killing effect on cancer cells. The CAP can inhibit tumor inflammatory responses and activate the immune system by reducing the expression of the key inflammatory factor Interleukin-6 (IL-6). However, the influence of the strong alternating electric field induced by CAP on the conformation and function of IL-6 remains unclear. In this study molecular dynamics simulation is used to investigate the effects of alternating electric fields with different frequencies and intensities on the conformation of IL-6. We statistically analyze the root mean square fluctuations, root mean square deviation, secondary structural alterations, and dipole moment changes of IL-6 under different electric field parameters. Furthermore, molecular docking is utilized to assess the influence on the receptor-binding process. The results show that when the electric field frequency is below 30 MHz and the intensity exceeds 0.5 V/nm, the average dipole moment of IL-6 increases, leading to changes in the rigid regions at the C-terminus which maintain structural stability. Specifically, the salt bridges that stabilize the long helices rupture, and the number of α-helices decreases. The docking outcomes reveal that the distance between the key binding residues of the conformationally altered IL-6 and its receptor increases, thereby disrupting the normal binding process and potentially impairing its normal biological functionality. This study explains the internal interaction mechanism of CAP-induced electric fields affecting IL-6-related biological effects at the micro level, and provides important theoretical basis for optimizing parameters in the practical application of CAP in tumor inflammation treatment and the development of effective cancer therapy strategies.
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Keywords:
- cold atmospheric plasma /
- alternating electric filed /
- interleukin-6 /
- molecular dynamics simulation
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[41] 赵伟, 杨瑞金, 张文斌, 华霄, 唐亚丽 2011 食品科学 32 91Google Scholar
Zhao W, Yang R J, Zhang W B, Hua X, Tang Y L 2011 Food Sci. 32 91Google Scholar
[42] Leebeek F W, Kariya K, Schwabe M, Fowlkes D M 1992 J. Biol. Chem. 267 14832Google Scholar
[43] Fontaine V, Savino R, Arcone R, de Wit L, Brakenhoff J P, Content J, Ciliberto G 1993 Eur. J. Biochem. 211 749Google Scholar
[44] Yang Z H, Xiao A, Liu D W, Shi Q, Li Y 2023 Plasma Process Polym. 20 2200242Google Scholar
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[1] Yan D, Sherman J H, Keidar M 2017 Oncotarget 8 15977Google Scholar
[2] Graves D B 2014 Phys. Plasmas 21 080901Google Scholar
[3] Limanowski R, Yan D, Li L, Keidar M 2022 Cancers (Basel) 14 3461Google Scholar
[4] Dubuc A, Monsarrat P, Virard F, et al. 2018 Ther. Adv. Med. Oncol. 10 1Google Scholar
[5] 张浩, 张基珅, 许德晖, 刘定新, 荣命哲 2023 电工技术学报 38 231Google Scholar
Zhang H, Zhang J K, Xu D H, Liu D X, Rong M Z 2023 Trans. China Electrotech. Soc. 38 231Google Scholar
[6] Dai X, Wu J, Lu L, Chen Y 2023 Biomolecules & Therapeutics 31 496Google Scholar
[7] 胡笑钏, 张晓伟, 刘样溪, 周古翔, 吕毅 2022 中国肝胆外科杂志 28 6Google Scholar
Hu X C, Zhang X W, Liu Y X, Zhou G X, Lü Y 2022 Chin. J. Hepatobil. Surg. 28 6Google Scholar
[8] Li Y, Tang T Y, Lee H J, Song K 2021 Int. J. Mol. Sci. 22 3956Google Scholar
[9] Dejonckheere C S, Torres-Crigna A, Layer J P, et al. 2022 Pharmaceutics 14 1767Google Scholar
[10] Schuster M, Seebauer C, Rutkowski R, et al. 2016 J. Craniomaxillofac. Surg. 44 1445Google Scholar
[11] Hirasawa I, Odagiri H, Park G, Sanghavi R, Oshita T, Togi A, Yoshikawa K, Mizutani K, Takeuchi Y, Kobayashi H, Katagiri S, Iwata T, Aoki A 2023 Plos One 18 e0292267Google Scholar
[12] Yusupov M, Van der Paal J, Neyts E C, Bogaerts A 2017 Bba-Gen Subjects 1861 839Google Scholar
[13] Jin X R, Hu X C, Chen J Y, Shan L Q, Hao D J, Zhang R 2024 J. Biomol. Struct. Dyn. DOI: 10.1080/07391102.2024.2329288
[14] Negi M, Kaushik N, Lamichhane P, Jaiswal A, Borkar S B, Patel P, Singh P, Ha Choi E, Kaushik N K 2024 J. Hazard. Mater. 472 134562Google Scholar
[15] Song M H, Tang Y, Cao K M, Qi L, Xie K P 2024 Front. Endocrinol. 15 1408312Google Scholar
[16] Zhao H K, Wu L, Yan G F, Chen Y, Zhou M Y, Wu Y Z, Li Y S 2021 Signal. Transduct. Tar. 6 263Google Scholar
[17] Wolf J, Rose-John S, Garbers C 2014 Cytokine 70 11Google Scholar
[18] Akbari Z, Saadati F, Mahdikia H, Freund E, Abbasvandi F, Shokri B, Zali H, Bekeschus S 2021 Appl. Sci. 11 4527Google Scholar
[19] Fu L, Fung F K, Lo A C, Chan Y K, So K F, Wong I Y, Shih K C, Lai J S 2018 Transl. Vis. Sci. Technol. 7 7Google Scholar
[20] 覃建锋, 宋海旺, 孙宝飞, 吉杨丹, 龙思方, 杨丹 2024 解剖学报 55 260Google Scholar
Tan J F, Song H W, Sun B F, Ji Y D, Long S F, Yang D 2024 Acta Anatom. Sin 55 260Google Scholar
[21] Filipe H A L, Loura L M S 2022 Molecules 27 2105Google Scholar
[22] Wu X, Xu L Y, Li E M, Dong G 2022 Chem. Biol. Drug. Des. 99 789Google Scholar
[23] 孙远昆, 郭良浩, 王凯程, 王少萌, 宫玉彬 2021 70 248701Google Scholar
Sun Y K, Guo L H, Wang K C, Wang S M, Gong Y B 2021 Acta Phys. Sin. 70 248701Google Scholar
[24] Zhang Q, Shao D Q, Xu P, Jiang Z T 2022 Polymers-Basel 14 123Google Scholar
[25] Fallah Z, Jamali Y, Rafii-Tabar H 2016 Plos One 11 e0166412Google Scholar
[26] Hu X, Jin X, Xing R, Liu Y, Feng Y, Lyu Y, Zhang R 2023 Results in Physics 51 106621Google Scholar
[27] 周晗, 耿轶钊, 晏世伟 2024 73 048701Google Scholar
Zhou H, Geng Y, Yan S 2024 Acta Phys. Sin. 73 048701Google Scholar
[28] Gupta M, Ha K, Agarwal R, Quarles L D, Smith J C 2021 Proteins 89 163Google Scholar
[29] Schillinger O, Panwalkar V, Strodel B, Dingley A J 2017 J. Phys. Chem. B 121 8113Google Scholar
[30] Arisi M, Soglia S, Pisani E G, et al. 2021 Dermatology Ther. 11 855Google Scholar
[31] Uchida G, Ito T, Ikeda J, Suzuki T, Takenaka K, Setsuhara Y 2018 Jpn. J. Appl. Phys. 57 096201Google Scholar
[32] Lin A, Truong B, Patel S, Kaushik N, Choi E H, Fridman G, Fridman A, Miller V 2017 Int. J. Mol. Sci. 18 966Google Scholar
[33] Hu Q, Joshi R P, Schoenbach K H 2005 Phys. Rev. E 72 031902Google Scholar
[34] Pronk S, Páll S, Schulz R, et al. 2013 Bioinformatics 29 845Google Scholar
[35] Huang J, MacKerell A D 2013 J. Comput. Chem. 34 2135Google Scholar
[36] Bussi G, Donadio D, Parrinello M 2007 J. Chem. Phys. 126 014101Google Scholar
[37] Parrinello M, Rahman A 1981 J. Appl. Phys. 52 7182Google Scholar
[38] Cheng T M, Blundell T L, Fernandez-Recio J 2007 Proteins 68 503Google Scholar
[39] Biggin P C, Smith G R, Shrivastava I, Choe S, Sansom M S 2001 Biochim. Biophys. Acta 1510 1Google Scholar
[40] Urabe G, Katagiri T, Katsuki S 2020 Bioelectricity 2 33Google Scholar
[41] 赵伟, 杨瑞金, 张文斌, 华霄, 唐亚丽 2011 食品科学 32 91Google Scholar
Zhao W, Yang R J, Zhang W B, Hua X, Tang Y L 2011 Food Sci. 32 91Google Scholar
[42] Leebeek F W, Kariya K, Schwabe M, Fowlkes D M 1992 J. Biol. Chem. 267 14832Google Scholar
[43] Fontaine V, Savino R, Arcone R, de Wit L, Brakenhoff J P, Content J, Ciliberto G 1993 Eur. J. Biochem. 211 749Google Scholar
[44] Yang Z H, Xiao A, Liu D W, Shi Q, Li Y 2023 Plasma Process Polym. 20 2200242Google Scholar
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