Tumor cells (murine melanoma) and human fibroblasts were simultaneously exposed to the chemotherapeutic agent etoposide (VP-16) and a static electric field (SEF) in a single or combinatory therapy. Single exposure to a SEF showed no significant differences in cell viability, whereas the combination with VP-16 induced apoptosis increases in both cell lines. Single VP-16 treatment induced apoptosis for up to 6 h, while the combination of both VP-16 and SEF extended apoptotic activity throughout for up to 24 h of exposure. The combined results of SEF with VP-16 induced a substantial increase of cell deaths, reducing VP-16 IC 50 from 13 µM to 5.1 µM in melanoma cells, and from 12.6 µM to 3.2 µM in the fibroblast cells. Detection of apoptosis via Anexina V/PI and caspase 3 showed a 100% marks increase. Taken all together, the present results strongly indicate that SEF dramatically increases VP-16 apoptosis, which makes this physical agent a strong chemotherapeutic sensitizer.
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