Malihe Keykhapour, Javad Baharara, Hamed Hatami, Maryam Lotfi, Sajad Farrokhyar,
Volume 27, Issue 3 (7-2024)
Abstract
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.
