Cell Death and Induced p53 Expression in Oral Cancer, HeLa, and Bone Marrow Mesenchyme Cells under the Exposure to Noncontact Electric Fields

Abstract

Background: p53 acts as a transcription factor to regulate the expression of genes that modulate various cellular activities. The proliferation of cancer cells has been inhibited under the exposure to low-intensity (18 peak-to-peak voltage) and intermediate-frequency (100 KHz) electric fields generated between 2 capacitive electrodes. Therefore, the aims of this study were to observe the molecular mechanism of cell death caused by noncontact electric field exposure and to determine whether p53 protein can serve as a biomarker for this exposure or not. Methods: Oral squamous cell carcinoma, HeLa, and bone marrow mesenchyme cells were exposed to noncontact electric fields of Electro-Capacitive Cancer Therapy (ECCT) for 24 h. To observe the mechanism of cell death caused by ECCT, immunocytochemistry of p53 was performed, and the p53 expression was evaluated using immunoreactive score (IRS) calculation. Results: Electric field exposure by ECCT increased the percentage of dead cells in oral cancer cells (18.39%), HeLa cells (6.60%), and bone marrow mesenchyme cells (34.05%) with statistical significance using the independent t test compared to each control group. The IRS of p53 in oral cancer, HeLa, and bone marrow mesenchyme cultures were 10.50, 11.25, and 4.94, respectively. Conclusion: The high IRS shown in the treated oral cancer and HeLa culture cells may suggest that p53 expression in these culture cells is associated with the cell death mechanism induced by the exposure to noncontact electric fields, and the increased cell death in these culture cells may correlate with the IRS.

CCL2 and IL18 expressions may associate with the anti-proliferative effect of noncontact electro capacitive cancer therapy in vivo

“…In the current study, anti-proliferative activity can be seen in Figure 3A, B and I, which revealed that ECCT exposure enables inhibition of breast tumor cell proliferation (p<0.001). This result is consistent with previous findings 1,2 . In addition, Giladi et al 5 exposed TTFields 150 kHz on non-small cell lung cancer cell lines and KLN205 squamous cell carcinoma in mice, which revealed inhibition of cancer cell viability and lung robust tumor growth due to the effect of AC-EF (TTFields) treatment.…”

“…In this study, we evaluated the effect of ECCT treatment as an anti-proliferative agent using an intermediate frequency of 150 kHz. Previous studies examined the anti-proliferative effects using several types of cancer cell lines and measurement of tumor size in vivo 1,2 . In the current study, anti-proliferative activity can be seen in Figure 3A, B and I, which revealed that ECCT exposure enables inhibition of breast tumor cell proliferation (p<0.001).…”

“…This result is consistent with the effect of reducing cell proliferation (using PCNA cell proliferation marker) in the IT group. Mujib et al 2 suggested that p53 might be involved in apoptosis induction in several cancer cell lines via a caspase-dependent apoptosis mechanism after exposure to ECCT. The results shown by the present study need to be confirmed with other protein markers involved in the tumor cell death mechanism.…”

“…Furthermore, this EF therapy could reduce the tumor size of C3H mice-breast tumor model, without abnormality in the dermal tissue and mammary glands of sham mice 1 . Moreover, Mujib et al 2 suggested that ECCT exposure (100-200 kHz) might induce p53 expression in cancer cells, such as oral squamous cell carcinoma, HeLa, and bone marrow mesenchyme cells. A previous study, using Tumor Treating Electric Field (TTFields) demonstrated that AC-EF with low intensity and intermediate frequency exposure to tumor cells caused the failure of tumor cell division toward the mitotic phase 3,4 .…”

CCL2 and IL18 expressions may associate with the anti-proliferative effect of noncontact electro capacitive cancer therapy in vivo

“…Moreover, Mujib et al . 2 suggested that ECCT exposure (100–200 kHz) might induce p53 expression in cancer cells, such as oral squamous cell carcinoma, HeLa, and bone marrow mesenchymal cells. A previous study, using Tumor Treating Electric Field (TTFields) demonstrated that AC-EF with low intensity and intermediate frequency exposure to tumor cells caused the failure of tumor cell division toward the mitotic phase 3 , 4 .…”