| Popis: |
Background: Focus on application of non-ionizing, extremely low frequency magnetic fields (ELF-EMF) as an alternative approach for treating cancer is rapidly rising nowadays. Nevertheless, little is known about the underlying anti-tumoral mechanism of action of them. Methods: In the present study, for the first time, we reported that along with apoptosis, 2 h/day exposure to 100 Hz, 1 mT ELF-EMF for a 5-day period, can induce necroptosis, a specific type of programed necrotic cell death, by promoting RIPK1/RIPK3/MLKL pathway which may also be responsible for observed pro-inflammatory responses in vivo, evident from an increase in plasma levels of pro-inflammatory cytokines including TNF-α, IL-1β, IL-2, IL-6, IL-17A and IFN-γ. Alongside, 30-day exposure to this system could also significantly suppress tumor growth and expression of markers of tumor cell proliferation, angiogenesis, and metastasis, namely Ki-67, CD31, VEGFR2 and MMP-9. Results: The number of tumor infiltrating lymphocytes (TILs), especially CD8+ Th cells were significantly increased following exposure to ELF-EMF. Interestingly, pretreating cancer cells with N-acetyl cysteine, a free-radical scavenger, or verapamil, an L-type calcium channel blocker in vitro, could diminish observed necroptotic and apoptotic responses while pretreating with calcium chloride, could aggravate responses.Conclusions: Overall, results of present study demonstrated that along with apoptosis, necroptosis is also a prominent form of cell death induced by exposure to ELF-EMF which is also dependent on elevated intracellular levels of ROS and calcium. |
