Title: Abstract 3543: Alternating electric fields (TTFields) induce autophagy in human cancer cell lines
Abstract: Abstract Tumor treating fields (TTFields) are an established anti-neoplastic treatment modality in patients with glioblastoma. TTFields are delivered via noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to the region of the tumor. Previous studies have shown that TTFields lead to increased granularity in treated cells. Granular or vesicular structures can indicate the formation of autophagosomes which are key structures in autophagy. Autophagy has been shown to regulate cell survival and proliferation under stress conditions and, in certain cases, influence cellular response to cytotoxic drugs. The goal of this study was to evaluate the possible effect of TTFields on the induction of autophapgy in treated cells. Different cancerous cell lines were treated with TTFields using the inovitro system. Cellular granularity was evaluated using flow cytometry. Autophagy was monitored by quantifying Lipidated Microtubule Associated Protein Light Chain 3 (LC3-II, a consensus marker for autophagosomes) levels using immunoblotting and immunofluorescence microscopy. Transmission Electron Microscopy (TEM) was used to visualize autophagosome-like structures. Flow cytometry analysis demonstrated that TTFields application leads to a significant increase in cellular granularity in all tested cell lines (up to 40%, P<0.05). Significant elevation in LC3-II levels was observed in treated U-87 MG cells using immunoblotting analysis (37%, P = 0.01). Evidence of increased autophagy following TTFields application was also detected using fluorescence microscopy, where punctate distribution of LC3-II was observed. TEM micrographs demonstrated the presence of autophagy typical, autophagosome-like structures in TTFields treated cells. TTFields are known to exert anti-mitotic effects by disrupting highly dipolar structures which play critical roles in mitosis. Our results suggest that in addition, TTFields can also induce cellular autophagy. Future studies are warranted to examine to what extent TTFields-elicited- autophagy may affect treatment outcomes, and to investigate the therapeutic implications of combining TTFields with autophagy inhibitors. Citation Format: Yaara Porat, Anna Shteingauz, Moshe Giladi, Rosa S. Schneiderman, Tali Voloshin, Mijal Munster, Roni Blat, Eilon D. Kirson, Uri Weinberg, Yoram Palti. Alternating electric fields (TTFields) induce autophagy in human cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3543.
Publication Year: 2016
Publication Date: 2016-07-15
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 2
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