Glioblastoma (GBM) is the most aggressive and lethal form of
brain cancer. Standard
therapies are non-specific and often of limited effectiveness; thus, efforts are underway to uncover novel, unorthodox
therapies against GBM. In previous studies, we investigated
Withaferin A, a steroidal
lactone from
Ayurvedic medicine that inhibits proliferation in
cancers including GBM. Another novel approach,
tumor treating fields (TTFields), is thought to disrupt mitotic spindle formation and stymie proliferation of actively dividing cells. We hypothesized that combining TTFields with
Withaferin A would synergistically inhibit proliferation in
glioblastoma. Human
glioblastoma cells (GBM2, GBM39, U87-MG) and human breast
adenocarcinoma cells (MDA-MB-231) were isolated from primary
tumors. The
glioma cell lines were genetically engineered to express
firefly luciferase. Proliferative potential was assessed either by bioluminescence imaging or cell counting via hemocytometer. TTFields (4 V/cm) significantly inhibited growth of the four
cancer cell lines tested (n = 3 experiments per time point, four measurements per sample, p < 0.02 at least; 2-way ANOVA, control vs. treatment). The combination of
Withaferin A (10-100 nM) with TTFields significantly inhibited the growth of the
glioma cells to a degree beyond that of
Withaferin A or TTFields alone. The interaction of the
Withaferin A and TTFields on
glioma cells was found to be synergistic in nature (p < 0.01, n = 3 experiments). These findings were validated by both bioluminescence and hemocytometric measurements. The combination of
Withaferin A with TTFields represents a novel approach to treat GBM in a manner that is likely better than either treatment alone and that is synergistic.