Volume 27, Issue 3 (7-2024)                   J Arak Uni Med Sci 2024, 27(3): 137-145 | Back to browse issues page


XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Keykhapour M, Baharara J, Hatami H, Lotfi M, Farrokhyar S. Assessment of the Anti-Cancer Properties of Harmine and Low-Frequency Electromagnetic Field (50 Hz) on Ovarian Cancer Cells (A2780). J Arak Uni Med Sci 2024; 27 (3) :137-145
URL: http://jams.arakmu.ac.ir/article-1-7674-en.html
1- Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Mashhad, Iran
2- Department of Biology and Research Center for Animal Development Applied Biology, Mashhad Branch Islamic Azad University, Mashhad, Iran , baharara@yahoo.com
3- Department of Hematology, Samen- Al- Aimah Hospital, North Khorasan Social Security Organization, Bojnurd, Iran
4- Department of Biology and Research Center for Animal Development Applied Biology, Mashhad Branch Islamic Azad University, Mashhad, Iran
Abstract:   (414 Views)
Introduction: Harmine is an alkaloid from the carboline family, belonging to the harmal plant, which has extensive applications in traditional medicine, with numerous studies highlighting its anti-cancer effects. Since biological processes are influenced by electromagnetic fields, the current study examined the anti-cancer effects of harmine and low-frequency electromagnetic fields on the expression of COX2, VEGF, and MMP-2 genes in the A2780 cell line.
Methods: In this experimental-laboratory study, ovarian cancer cell lines were randomly divided into four groups: control, harmine at concentrations of 6, 12, 24, 48, 96, and 192 micromolar, low-frequency electromagnetic field with an intensity of 50 Gauss, and harmine at a concentration of 48 micromolar with a low-frequency electromagnetic field of 50 Gauss intensity. Their toxicity was assessed using the MTT assay, nuclear morphological changes by DAPI staining, apoptotic effects of these compounds by measuring nitric oxide (NO), and gene expression changes by Real-Time PCR. Quantitative data were analyzed the ANOVA statistical test at a P < 0.05 level.
Results: Quantitative data comparison of this research indicated that harmine and a low-frequency electromagnetic field with an intensity of 50 Gauss caused a concentration-dependent reduction in the viability of ovarian cancer cells. Additionally, in the nitric oxide test, a significant decrease was found in the control group compared to the groups treated with a concentration of 48 micromolar and synergized with a 50 Gauss electromagnetic field (p<0.05). The expression of the aforementioned genes in treated cells showed a significant decrease. Treating ovarian cancer cells with harmine and its combined application led to significant nuclear morphological changes, including chromatin condensation, formation of apoptotic bodies, and wrinkling of the cell membrane.
Conclusions: The combined application of harmine and a low-frequency electromagnetic field induced apoptosis in A2780 cancer cells and resulted in the downregulation of COX2, VEGF-A, and MMP-2 gene expression. Consequently, the combined use of harmine with a low-frequency electromagnetic field, due to its effective cytotoxicity in inhibiting proliferation and inducing apoptosis, could be a suitable candidate for clinical studies.
Full-Text [PDF 1369 kb]   (163 Downloads) |   |   Full-Text (HTML)  (32 Views)  
Type of Study: Original Atricle | Subject: Basic Sciences
Received: 2024/03/17 | Accepted: 2024/07/7

References
1. Mirzaie A, Diba H, Khosravi-Nejad F, Javanmardi H. Synergistic cytotoxicity of bevacizumab and silver nanoparticles on ovarian cancer cell line (A2780) and analysis of Bcl-2 and caspase 3 apoptotic genes expression [in Persian]. Cell and Tissue Journal. 2021;12(2):72-8. doi: 10.52547/JCT.12.2.72
2. Guo H, Xue W, Zhao Q, Zhao H, Hu Z, Zhang X, Duan GJJoCS. Correlation and significance of COX-2, Ki67, VEGF and other immune indexes with the growth of malignant pulmonary nodules. J Cardiothorac Surg. 2022;17(1):290. pmid: 36384712 doi: 10.1186/s13019-022-02039-7
3. Masoumi-Dehghi S, Babashah S, Sadeghizadeh M. microRNA-141-3p-containing small extracellular vesicles derived from epithelial ovarian cancer cells promote endothelial cell angiogenesis through activating the JAK/STAT3 and NF-κB signaling pathways. J Cell Commun Signal. 2020;14(2):233-44.
4. Chen S-M, Jahejo AR, Nabi F, Ahmed S, Zhao J-f, Yu J, et al. Janus kinase/signal transducer and activator of transcription signaling pathway-related genes STAT3, SOCS3 and their role in thiram induced tibial dyschondroplasia chickens. Res Vet Sci. 2021;136:25-31.
5. Sanaei Jahromi M, Kavousi F. Evaluation of the effect of valproic acid on JAK/STAT pathway, SOCS1, SOCS3, Bcl-xL, c-Myc, and Mcl-1 gene expression, cell growth inhibition and apoptosis induction in human colon cancer HT29 cell line [in Persian]. Armaghan-e Danesh. 2021;26(3):324-37. doi: 10.52547/armaghanj.26.3.324
6. Alasvand M, Assadollahi V, Ambra R, Hedayati E, Kooti W, Peluso IJOm, longevity c. Antiangiogenic effect of alkaloids. Oxid Med Cell Longev. 2019, 2019:9475908. pmid: 31178979 doi: 10.1155/2019/9475908
7. Adamski Z, Blythe LL, Milella L, Bufo SA. Biological activities of alkaloids: from toxicology to pharmacology. Toxins (Basel). 2020;12(4):210. pmid: 32224853 doi: 10.3390/toxins12040210
8. Wink M. Annual plant reviews, biochemistry of plant secondary metabolism. Hoboken, NJ: John Wiley & Sons; 2011.p.99-1177.
9. Geng X, Ren Y, Wang F, Tian D, Yao X, Zhang Y. Harmines inhibit cancer cell growth through coordinated activation of apoptosis and inhibition of autophagy. Biochem Biophys Res Commun. 2018;498(1):99-104. pmid: 29501493 doi: 10.1016/j.bbrc.2018.02.205
10. Chitbandi R, Baharara J, Tehranipour M. Apoptosis induction of harmine on human colon cancer cell line HT29 and alteration in apoptotic genes expression P53, Bax and Bcl-2 [in Persian]. Journal of Animal Biology 2022;14(4):51-63.
11. Roshankhah S, Arji Rodsari B, Jalili C, Salahshoor MR. The
12. role of harmine in up-regulating p53 gene expression and inducing apoptosis in MCF-7 cell line [in Persian]. Middle East Journal of Cancer. 2020;11(1):34-41. doi: 10.30476/mejc.2019.78703.0
13. Moshtaghi S, Parivar K, Baharara J, Hayati N, Kerachian MA. Synergic application effects of bromelain and low-frequency electromagnetic field on the aortic ring on angiogenesis [in Persian]. Journal of Plasma and Biomarkers. 2019;12(1):13-24.
14. Barati M, Darvishi B, Javidi MA, Mohammadian A, Shariatpanahi SP, Eisavand MR, et al. Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis. Cell Prolif. 2021;54(12):e13154. pmid: 34741480 doi: 10.1111/cpr.13154
15. Baharara J, Zahedifar Z. The effect of low-frequency electromagnetic fields on some biological activities of animals [in Persian]. J Arak Univ Med Sci. 2012;15(7):80-93.
16. Baharara J, Hadad F, Ashraf A, Khanderoo E. The effect of extremely low frequency electromagnetic field [50Hz] on induction of chromosomal damages on bone marrow erythrocytes of male Balb/C mouse] [in Persian]. J Arak Univ Med Sci 2008;11(2):19-26.
17. Maftoon M, Ahmadi R. The cytotoxic effect of progesterone on viability and Nitric oxide gene expression in fibroblastoma cells (L929) [in Persian]. Res Cell and Tissue. 2021;2(2):28-34.
18. Khezri S, Baharara J, Amini E. Evaluation of the effect of menthol on apoptosis induction and Bax and Bcl2 gene expression in the CT-26 colon cancer cell line[in Persian]. Cell and Tissue Journal. 2021;12(1):20-8. doi: 10.52547/JCT.12.1.20
19. Salek F, Baharara J, Nejad Shahrokhabadi K, Amini E. Comparison of the effect of exosomes derived from Sertoli cells with vitamin C on damage induced by electromagnetic field (50 Hz) in spermatogonial stem cells [in Persian]. Journal of Plasma and Biomarkers. 2021; 1:173:112-22.
20. Thawabteh A, Juma S, Bader M, Karaman D, Scrano L, Bufo SA, et al. The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens. Toxins (Basel). 2019;11(11):656.
21. Quintero-Fabián S, Arreola R, Becerril-Villanueva E, Torres-Romero JC, Arana-Argáez V, Lara-Riegos J, et al. Role of matrix metalloproteinases in angiogenesis and cancer. Front Oncol. 2019;9:1370. pmid: 31921634 doi: 10.3389/fonc.2019.01370
22. Ribatti D, Solimando AG, Pezzella F. The anti-VEGF (R) drug discovery legacy: improving attrition rates by breaking the vicious cycle of angiogenesis in cancer. Cancers (Basel). 2021;13(14):3433. pmid: 34298648 doi: 10.3390/cancers13143433
23. Caroline Vos M, van der Wurff AA, van Kuppevelt TH, Massuger LFAG. The role of MMP-14 in ovarian cancer: a systematic review. J Ovarian Res. 2021;14(1):101. pmid: 34344453 doi: 10.1186/s13048-021-00852-7
24. Carey P, Low E, Harper E, Stack MS. Metalloproteinases in ovarian cancer. Int J Mol Sci. 2021;22(7):3403. pmid: 33810259 doi: 10.3390/ijms22073403
25. Azevedo Martins JM, Rabelo-Santos SH, do Amaral Westin MC, Zeferino LC. Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A in cervical cancer patient survival: a competing risk analysis. BMC Cancer. 2020;20(1):660. pmid: 32669083 doi: 10.1186/s12885-020-07150-3
26. Miller F, Singh GJOEoCCotB. Cancer and Angiogenesis. NCI.
27. 2016:39-54.
28. Yetkin-Arik B, Kastelein AW, Klaassen I, Jansen CH, Latul YP, Vittori M, et al. Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy. Biochim Biophys Acta Rev Cancer. 2021;1875(1):188446. pmid: 33058997 doi: 10.1016/j.bbcan.2020.188446
29. Jin S-J, Song Y, Park HS, Park KW, Lee S, Kang HJL. Harmine Inhibits Multiple TLR-Induced Inflammatory Expression through Modulation of NF-κB p65, JNK, and STAT1. Life (Basel). 2022;12(12):2022. pmid: 36556387 doi: 10.3390/life12122022
30. Hooshyar M, Abedian-Kenari S, Mohammadpour A, Mirmajidi H, Jafari-Sabet M, Ataee R. Evaluation of NOS2 Polymorphism in Gastric Adenocarcinoma Patients in Mazandaran Province [in Persian]. jssu. 2021;29(6):3843-53. doi: 10.18502/ssu.v29i6.6994

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2025 CC BY-NC 4.0 | Journal of Arak University of Medical Sciences

Designed & Developed by : Yektaweb