Combined Effect of Plasma-Activated Water and Topotecan in Glioblastoma Cells

SIMPLE SUMMARY: New forms of cancer treatment are needed to target resistant cancers or reduce severe side effects associated with some treatments. Cold Atmospheric Plasma (CAP) has demonstrated promising anti-cancer effects in several types of cancer, not only by direct application onto cancer cells, but also by indirect treatment using activation of liquids, such as water. Although the exact mechanism of action and underlying signaling pathways are yet to be discovered, CAP has the potential to be combined with traditional therapies, such as chemotherapy. This study investigates a new approach for treating brain cancer by combining a conventional cancer drug with plasma-activated water, which is produced by exposing water to plasma. The reactive chemical species in these solutions may help to kill the cancer cells and reduce the amount of drug that is needed. Not only were the combined treatments able to interfere with cell metabolism and increase cell death, but they also reduced the long-term cell proliferation. This study provides evidence that indirect CAP-derived approaches could be used in combination with chemotherapeutics for prospective treatment of brain cancer. ABSTRACT: The increase in cancer diagnoses and cancer deaths, severe side effects of existing treatments and resistance to traditional treatments have generated a need for new anticancer treatments. Glioblastoma multiforme (GBM) is the most common, malignant and aggressive brain cancer. Despite many innovations regarding GBM treatment, the final outcome is still very poor, making it necessary to develop new therapeutic approaches. Cold atmospheric plasma (CAP) as well as plasma-activated liquids (PAL) are being studied as new possible approaches against cancer. The anticancer activity of PAL such as “plasma-activated water” (PAW) is dependent on the reactive chemical compounds present in the solution. Possible combinatory effects with conventional therapies, such as chemotherapeutics, may expand the potential of PAL for cancer treatment. We aim to explore the therapeutic properties of a combination of PAW and topotecan (TPT), an antineoplastic agent with major cytotoxic effects during the S phase of the cell cycle, on a GBM cancer cell line (U-251mg). Combined treatments with PAW and TPT showed a reduction in the metabolic activity and cell mass, an increase in apoptotic cell death and a reduction in the long-term survival. Single applications of PAW+TPT treatments showed a cytotoxic effect in the short term and an antiproliferative effect in the long term, warranting future exploration of combining PAW with chemotherapeutic agents as new therapeutic approaches.