Differential effects of cold atmospheric plasma in the treatment of malignant glioma

Siu, A., Volotskova, O., Cheng, X., Khalsa, S. S., Bian, K., Murad, F., & Sherman, J. H.

Cold atmospheric plasma (CAP) is a partially ionized gas that can focally deliver low levels of ultraviolet (UV) radiation and ionized particles to synergistically generate reactive oxygen species (ROS). This technology has demonstrated efficacy in several biomedical applications ranging from anti-bacterial decontamination to promotion of wound healing [1]. The anti-growth effects of CAP on prokaryotic cells are well established, but its effects on eukaryotic cell remain largely uncharacterized. Lower dosages (i.e. duration or power) of helium-CAP can stimulate detachment, migration, and proliferation in fibroblasts [2], endothelial [3,4] and smooth muscle cells in vitro [5,6]. Several studies investigating the role of CAP in various cancers have shown promise [7–10]. In addition, we recently showed that application of CAP can selectively induce apoptosis in various cancer cell lines in vitro and significantly reduce in vivo tumor size of a murine melanoma model [11]. Our group also recently demonstrated a key mechanism of cell cycle interference in malignant cells [12]. In specific, we have shown that CAP treatment induced a robust increase in the G2/M population in epidermal cancer cells but not in non-malignant cells in vitro.

Glioblastoma is a highly malignant primary central nervous system neoplasm associated with poor survival and is invariably fatal. It is considered one of the most aggressive forms of human cancers, characterized largely by its rapid growth, extensive angiogenesis, and invariable resistance to all current therapies. Consequently, treatments remain largely palliative despite recent advances with the integration of multi-modal therapies. The current standard of care, known as the Stupp protocol, improves median survival up to 14.6 months [13] with five-year survival at less than 10% [14].