Exth-25. Effects of Tumor Treating Fields (Ttfields) and Temozolomide in MGMT Expressing and Non-Expressing Patient-Derived Glioblastoma Cells

Clark, Paul A.; Gaal, Jordan T.

doi:10.1093/neuonc/now212.269

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our manuscript is the first report on synergistic interaction in therapy between TTFields with the natural product, Withaferin A. TTField application can sensitize glioblastoma stem cells from temozolomide-resistant patients towards temozolomide therapy [7, 27]. Several different TTField combination therapies with numerous cytostatic agents (metformin, mefloquine, ganciclovir, bumetanide, and minocycline) have been studied in glioma cell lines but in no treatment regimen was there more than an additive improvement in efficacy of the cytostatic [28] while statistical analysis in the current study indicated therapeutic synergy with co-treatments of Withaferin A and TTFields.…”

Section: Discussionmentioning

confidence: 99%

“…Such acceptance of therapy has prompted several lines of investigation into the combination of TTFields with established standard of care approaches such as temozolomide [7, 27], bevacizumab [8, 32, 33], and ionizing radiation [34]. The novel combination of TTFields with Withaferin A commands interest because of their synergistic interaction against human-derived glioma cell cultures.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Synergistic inhibition of glioma cell proliferation by Withaferin A and tumor treating fields

et al. 2017

View full text Add to dashboard Cite

BACKGROUND 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. METHODS 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. RESULTS TTFields (4 V/cm) significantly inhibited growth of the four cancer cell lines tested (n=3 experiments per time point, 4 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. CONCLUSIONS 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.

show abstract

Section: Discussionmentioning

confidence: 99%