Non-Contact Electro Capacitive Cancer Therapy (ECCT) Modulate the mRNA Expression of PDGF and IL-1 in DMBA-induced Breast Cancer Rat

  • Nurul Hidayah Biotechnology Departement, Institut Karya Mulia Bangsa (IKMB), Semarang, Indonesia
  • Feby Nur Sakinah Stem Cell and Cancer Research (SCCR) Laboratory, Semarang, Indonesia
  • Dyah Retno Annisa Student of Biology Graduate Program, Faculty of Biology, Universitas Gadjah Mada (UGM), Yogyakarta, 55281, Indonesia
Keywords: Breast Cancer, ECCT, PDGF, IL-1, Gene Expression

Abstract

Background: Breast cancer remains the most prevalent cancer among women globally, with significant mortality rates. Traditional therapies, such as surgery, chemotherapy, and radiotherapy, are associated with severe side effects and resistance, highlighting the need for alternative treatments. Electro-Capacitive Cancer Therapy (ECCT) is a promising non-invasive approach that uses low-intensity electric fields to selectively target cancer cells. Objective: This study aims to investigate the molecular mechanisms of ECCT, particularly its effects on key molecules such as PDGF and IL-1 in a DMBA-induced rat breast cancer model. Materials and Methods: The study used a post-test-only control group design with four groups: NINT (normal tissue), NIT (untreated tumor tissue), INT (DMBA-induced tumor tissue), and IT (ECCT-treated tumor tissue). ECCT was applied at 150 kHz for 21 days. mRNA expressions of PDGF and IL-1 were quantified using quantitative RT-PCR. Results: ECCT significantly reduced the mRNA expression of PDGF and IL-1 in treated tumor tissues (IT) compared to untreated tumor tissues (INT), bringing their levels closer to those observed in normal tissue (NINT). This suggests that ECCT downregulates key pro-angiogenic and pro-inflammatory molecules involved in tumor progression. Conclusion: In conclusion, the non-contact ECCT with a frequency of 150 kHz might downregulate PDGF and IL-1 mRNA expression in rat breast tumor tissue.

References

1. Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, et al. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis [Internet]. Vol. 5, Genes and Diseases. Chongqing yi ke da xue, di 2 lin chuang xue yuan Bing du xing gan yan yan jiu suo; 2018 [cited 2021 Apr 23]. p. 77–106. Available from: http://creativecommons.org/licenses/by-nc-nd/4.0/
2. Dibden A, Offman J, Duffy SW, Gabe R. cancers Worldwide Review and Meta-Analysis of Cohort Studies Measuring the Effect of Mammography Screening Programmes on Incidence-Based Breast Cancer Mortality. Available from: www.mdpi.com/journal/cancers
3. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J for. 2020;
4. Torre LA, Islami F, Siegel RL, Ward EM, Jemal A. Global cancer in women: Burden and trends. Cancer Epidemiol Biomarkers Prev. 2017;26(4):444–57.
5. Tao Z, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast Cancer: Epidemiology and Etiology. Cell Biochem Biophys. 2013;
6. Tao ZQ, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast Cancer: Epidemiology and Etiology. Cell Biochem Biophys. 2015 Jun 15;72(2):333–8.
7. Dittmer J. Breast cancer stem cells: Features, key drivers and treatment options. Vol. 53, Seminars in Cancer Biology. Academic Press; 2018. p. 59–74.
8. Palomeras S, Ruiz-Martínez S, Puig T. molecules Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance. 2018 [cited 2021 Feb 10]; Available from: www.mdpi.com/journal/molecules
9. Sahoo D, Mitra T, Chakraborty K, Sarkar P. Remotely controlled electro-responsive on-demand nanotherapy based on amine-modified graphene oxide for synergistic dual drug delivery. Mater Today Chem. 2022 Sep 1;25:100987.
10. Pratiwi R, Yudi Antara N, Gunawan Fadliansyah L, Arif Ardiansyah S, Nurhidayat L, Nurwening Sholikhah E, et al. Open Peer Review CCL2 and IL18 expressions may associate with the anti-proliferative effect of noncontact electro capacitive cancer therapy in vivo [version 1; peer review: awaiting peer review]. 2019 [cited 2022 Jul 15]; Available from: https://doi.org/10.12688/f1000research.20727.1
11. You D, Jang MJ, Lee J, Suh N, Jeong IG, Sohn DW, et al. Comparative analysis of periprostatic implantation and intracavernosal injection of human adipose tissue-derived stem cells for erectile function recovery in a rat model of cavernous nerve injury. Prostate. 2013;73(3):278–86.
12. Kim EH, Song HS, Yoo SH, Yoon M. Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis. Oncotarget. 2016;7(40):65125–36.
13. Nismayanti A, Baidillah MR, Triwikantoro, Endarko, Taruno WP. Wire-mesh capacitance tomography for treatment planning system of electro-capacitive cancer therapy. J Teknol. 2021;83(6):109–15.
14. Alamsyah F, Pratiwi R, Firdausi N, Mesak Pello JI, Evi S, Nugraheni D, et al. Cytotoxic T cells response with decreased CD4/CD8 ratio during mammary tumors inhibition in rats induced by non-contact electric fields [version 1; peer review: 1 approved, 1 approved with reservations] report report. 2021; Available from: https://doi.org/10.12688/f1000research.27952.1
15. Andiani L, Al Huda M, Purwo Taruno W. ISSN: 2279-7165-Available on-line at www.embj.org EUROMEDITERRANEAN BIOMEDICAL JOURNAL. 2017 [cited 2021 Apr 21];12(38):178–83. Available from: www.embj.org
16. Mujib SA, Alamsyah F, Purwo Taruno W. Cell Death and Induced p53 Expression in Oral Cancer, HeLa, and Bone Marrow Mesenchyme Cells under the Exposure to Noncontact Electric Fields. Integr Med Int [Internet]. 2017 [cited 2021 Apr 23];4:161–70. Available from: www.karger.com/imiwww.karger.com/imi
17. Alamsyah F, Fadhlurrahman AG, Pello JI, Firdausi N, Evi S, Karima FN, et al. PO-111 Non-contact electric fields inhibit the growth of breast cancer cells in animal models and induce local immune reaction. ESMO Open. 2018 Jun;3:A269.
18. Dominguez-Brauer C, Thu KL, Mason JM, Blaser H, Bray MR, Mak TW. Targeting Mitosis in Cancer: Emerging Strategies. Mol Cell. 2015;60(4):524–36.
19. Pu X, Storr SJ, Zhang Y, Rakha EA, Green AR, Ellis IO, et al. Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival. Apoptosis [Internet]. 2017 Mar 31 [cited 2021 Feb 1];22(3):357–68. Available from: http://link.springer.com/10.1007/s10495-016-1323-5
20. Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S, et al. Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. Nat Med [Internet]. 2018;24(4):463–73. Available from: http://dx.doi.org/10.1038/nm.4494
21. Wang J, Wu L-L, Zhang Y, Purnami SW, Putra RS, Edina AI, et al. You may also like Establishing a survival prediction model for esophageal squamous cell carcinoma based on CT and histopathological images Cox Model Survival Analysis to Evaluate Treatment of Electro-Capacitive Cancer Therapy (ECCT) For Cancer Patients. J Phys. 2021;12036.
22. Andiani L, Endarko, Al Huda M, Taruno WP. A novel method for analyzing electric field distribution of electro capacitive cancer treatment (ECCT) using wire mesh electrodes: A case study of brain cancer therapy. EuroMediterranean Biomed J. 2017;12(38):178–83.
23. Alamsyah F, Niswah Ajrina I, Nur F, Dewi A, Iskandriati D, Prabandari SA, et al. Antiproliferative Effect of Electric Fields on Breast Tumor Cells In Vitro and In Vivo. Indones J Cancer Chemoprevention [Internet]. 2015 Oct 31 [cited 2021 Apr 22];6(3):71–7. Available from: https://www.ijcc.chemoprev.org/index.php/ijcc/article/view/88
24. Efek Terapi Electro-Capacitive Cancer Therapy (ECCT) terhadap Profil Leukosit dan Rasio CD4+/CD8+ Sukarelawan Sehat [Internet]. [cited 2022 Jul 15]. Available from: http://etd.repository.ugm.ac.id/penelitian/detail/189145
25. Purnami SW, Putra RS, Edina AI, Pertiwi IN, Sukur E, Soraya N. Cox Model Survival Analysis to Evaluate Treatment of Electro-Capacitive Cancer Therapy (ECCT) For Cancer Patients. J Phys Conf Ser [Internet]. 2021 Mar 1 [cited 2022 Jul 5];1863(1):012036. Available from: https://iopscience.iop.org/article/10.1088/1742-6596/1863/1/012036
26. Pratiwi R, Antara NY, Fadliansyah LG, Ardiansyah SA, Nurhidayat L, Sholikhah EN, et al. CCL2 and IL18 expressions may associate with the anti-proliferative effect of noncontact electro capacitive cancer therapy in vivo. F1000Research [Internet]. 2020 Jul 23 [cited 2021 Mar 25];8:1770. Available from: https://doi.org/10.12688/f1000research.20727.1
27. Pratiwi R, Antara NY, Fadliansyah LG, Ardiansyah SA, Nurhidayat L, Sholikhah EN, et al. CCL2 and IL18 expressions may associate with the anti-proliferative effect of noncontact electro capacitive cancer therapy in vivo. F1000Research. 2019;8.
28. Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31–46.
29. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell [Internet]. 2011;144(5):646–74. Available from: http://dx.doi.org/10.1016/j.cell.2011.02.013
30. Tabl AA, Alkhateeb A, ElMaraghy W, Rueda L, Ngom A. A machine learning approach for identifying gene biomarkers guiding the treatment of breast cancer. Front Genet. 2019;10(MAR):256.
31. APAF-1 Is a Transcriptional Target of p53 in DNA Damage-induced Apoptosis | Cancer Research | American Association for Cancer Research [Internet]. [cited 2022 Jul 26]. Available from: https://aacrjournals.org/cancerres/article/61/18/6660/507965/APAF-1-Is-a-Transcriptional-Target-of-p53-in-DNA
32. Jemmerson R, Staskus K, Higgins L, Conklin K, Kelekar A. Intracellular leucine-rich alpha-2-glycoprotein-1 competes with Apaf-1 for binding cytochrome c in protecting MCF-7 breast cancer cells from apoptosis. Apoptosis [Internet]. 123AD [cited 2022 Jul 26];1:71–82. Available from: https://doi.org/10.1007/s10495-020-01647-9
33. Messeha SS, Zarmouh NO, Asiri A, Soliman KFA. Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells. Eur J Pharmacol. 2020 Oct 15;885.
34. Petrarca CR, Brunetto AT, Duval V, Brondani A, Carvalho GP, Garicochea B. Survivin as a predictive biomarker of complete pathologic response to neoadjuvant chemotherapy in patients with stage II and stage III breast cancer. Clin Breast Cancer [Internet]. 2011 Apr [cited 2021 Feb 11];11(2):129–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21569999
35. Jha K, Shukla M, Pandey M. Survivin expression and targeting in breast cancer [Internet]. Vol. 21, Surgical Oncology. Surg Oncol; 2012 [cited 2021 Feb 11]. p. 125–31. Available from: https://pubmed.ncbi.nlm.nih.gov/21334875/
36. Hwang B, Song JH, Park SL, Kim JT, Kim WJ, Moon SK. Carnosine impedes pdgf-stimulated proliferation and migration of vascular smooth muscle cells in vitro and sprout outgrowth ex vivo. Nutrients. 2020;12(9):1–18.
37. Ibaraki H, Kanazawa T, Kurano T, Oogi C, Takashima Y, Seta Y. Anti-RelA siRNA-Encapsulated Flexible Liposome with Tight Junction-Opening Peptide as a Non-invasive Topical Therapeutic for Atopic Dermatitis. Biol Pharm Bull. 2019;42(7):1216–25.
38. Luo LH, Rao L, Luo LF, Chen K, Ran RZ, Liu XL. Long non-coding RNA NKILA inhibited angiogenesis of breast cancer through NF-κB/IL-6 signaling pathway. Microvasc Res. 2020 May 1;129:103968.
39. Duffy MJ, O’donovan N, Brennan DJ, Gallagher WM, Ryan BM. Mini-review Survivin: A promising tumor biomarker. [cited 2022 Aug 16]; Available from: www.elsevier.com/locate/canlet
40. Jha K, Shukla M, Pandey M. Survivin expression and targeting in breast cancer. Vol. 21, Surgical Oncology. Elsevier; 2012. p. 125–31.
41. Penn JW, Grobbelaar AO, Rolfe KJ. The role of the TGF-β family in wound healing, burns and scarring: a review. Int J Burns Trauma [Internet]. 2012;2(1):18–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22928164%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3415964
42. Wang S, Mo M, Wang J, Sadia S, Shi B, Fu X, et al. Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property. Cell Mol Life Sci. 2018;75(3):547–61.
43. Shimabukuro-Vornhagen A, Draube A, Liebig TM, Rothe A, Kochanek M, Von Bergwelt-Baildon MS. The immunosuppressive factors IL-10, TGF-β, and VEGF do not affect the antigen-presenting function of CD40-activated B cells. J Exp Clin Cancer Res. 2012;31(1):1–7.
44. Song MH, Jo Y, Kim YK, Kook H, Jeong D, Park WJ. The TSP-1 domain of the matricellular protein CCN5 is essential for its nuclear localization and anti-fibrotic function. PLoS One [Internet]. 2022 Apr 1 [cited 2022 Jul 16];17(4):e0267629. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267629
45. Bornstein P. Thrombospondins function as regulators of angiogenesis. J Cell Commun Signal [Internet]. 2009 Oct 2 [cited 2022 Aug 17];3(3–4):189–200. Available from: https://link.springer.com/article/10.1007/s12079-009-0060-8
46. Livak KJ, Schmittgen TD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods. 2001 Dec 1;25(4):402–8.
47. Awasthi K, Chang FL, Hsieh PY, Hsu HY, Ohta N. Characterization of endogenous fluorescence in nonsmall lung cancerous cells: A comparison with nonmalignant lung normal cells. J Biophotonics [Internet]. 2020 May 1 [cited 2023 Jan 13];13(5):e201960210. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/jbio.201960210
48. Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis - The p53 network. J Cell Sci. 2003;116(20):4077–85.
49. Güllülü Ö, Hehlgans S, Rödel C, Fokas E, Rödel F. Tumor suppressor protein p53 and inhibitor of apoptosis proteins in colorectal cancer—a promising signaling network for therapeutic interventions. Cancers (Basel). 2021 Feb 2;13(4):1–22.
50. Imao T, Nagata S. Apaf-1- and Caspase-8-independent apoptosis. Cell Death Differ [Internet]. 2013 [cited 2022 Aug 16];20:343–52. Available from: www.nature.com/cdd
51. Alamsyah F, Pratiwi R, Firdausi N, Mesak Pello JI, Evi S, Nugraheni D, et al. Cytotoxic T cells response with decreased CD4/CD8 ratio during mammary tumors inhibition in rats induced by non-contact electric fields [version 1; peer review: 1 approved, 1 approved with reservations] report report. 2021 [cited 2021 Apr 21]; Available from: https://doi.org/10.12688/f1000research.27952.1
52. Chang J-W, Kuo W-H, Lin C-M, Chen W-L, Chan S-H, Meng •, et al. Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway. Oncogene [Internet]. 2018 [cited 2022 Jul 16];37:4137–50. Available from: https://doi.org/10.1038/s41388-018-0253-9
53. Ayoub NM, Jaradat SK, Al-Shami KM, Alkhalifa AE. Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches. Front Pharmacol. 2022;13(February):1–21.
54. Malekian S, Rahmati M, Sari S, Kazemimanesh M, Kheirbakhsh R, Muhammadnejad A, et al. Expression of Diverse Angiogenesis Factor in Different Stages of the 4T1 Tumor as a Mouse Model of Triple-Negative Breast Cancer. Adv Pharm Bull [Internet]. 2020 [cited 2022 Jul 16];2020(2):323–8. Available from: https://apb.tbzmed.ac.ir
55. Ren B, Yee KO, Lawler J, Khosravi-Far R. Regulation of tumor angiogenesis by thrombospondin-1. Biochim Biophys Acta - Rev Cancer. 2006 Apr 1;1765(2):178–88.
56. Gao Y, Wang Y, Yu J, Guo R. FGF Exhibits an Important Biological Role on Regulating Cell Proliferation of Breast Cancer When it Transports Into The Cell Nuclei. Cell Biochem Biophys. 2022;80(2):311–20.
57. Cheng SL, Liu RH, Sheu JN, Chen ST, Sinchaikul S, Tsay GJ. Toxicogenomics of A375 human malignant melanoma cells treated with arbutin. J Biomed Sci. 2007;14(1):87–105.
58. Awasthi K, Chang FL, Hsu HY, Ohta N. Cancer specific apoptosis induced by electric field: A possible key mechanism in cell-competition and photodynamic action. Sensors Actuators B Chem [Internet]. 2021;347(August):130635. Available from: https://doi.org/10.1016/j.snb.2021.130635
59. Moitra K. Overcoming Multidrug Resistance in Cancer Stem Cells. Biomed Res Int. 2015;2015.
60. Ruan W, Lim HH, Surana U. Mapping Mitotic Death: Functional Integration of Mitochondria, Spindle Assembly Checkpoint and Apoptosis. Front Cell Dev Biol. 2019 Jan 10;6:177.
61. Bakshi HA, Quinn GA, Nasef MM, Mishra V, Aljabali AAA, El-Tanani M, et al. Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways. Cells. 2022;11(9):1–15.
62. Peng L, Fu C, Wang L, Zhang Q, Liang Z, He C, et al. The Effect of Pulsed Electromagnetic Fields on Angiogenesis. Bioelectromagnetics. 2021 Apr 1;42(3):250–8.
63. Goto T, Fujioka M, Ishida M, Kuribayashi M, Ueshima K, Kubo T. Noninvasive up-regulation of angiopoietin-2 and fibroblast growth factor-2 in bone marrow by pulsed electromagnetic field therapy. J Orthop Sci [Internet]. 2010 [cited 2023 Jan 26];15(5):661–5. Available from: https://pubmed.ncbi.nlm.nih.gov/20953928/
64. Williams CD, Markov MS. THERAPEUTIC ELECTROMAGNETIC FIELD EFFECTS ON ANGIOGENESIS DURING TUMOR GROWTH: A PILOT STUDY IN MICE. http://dx.doi.org/101081/JBC-100108573 [Internet]. 2009 [cited 2023 Jan 26];20(3):323–9. Available from: https://www.tandfonline.com/doi/abs/10.1081/JBC-100108573
Published
2024-12-10
How to Cite
Hidayah, N., Sakinah, F. N., & Annisa, D. R. (2024). Non-Contact Electro Capacitive Cancer Therapy (ECCT) Modulate the mRNA Expression of PDGF and IL-1 in DMBA-induced Breast Cancer Rat. International Journal of Cell and Biomedical Science, 2(6), 210-216. https://doi.org/10.59278/cbs.v2i6.44
Section
Articles