Cold Atmospheric Plasma Suppresses Ovarian Cancer Cell Activity With Concurrent Secretion Of Heat Shock Protein 27 Affecting Monocyte Fate

Abstract

Background Ovarian cancer (OC) is a gynecologic tumor with poor prognosis. Despite radical cytoreductive surgery and platinum-based adjuvant systemic treatment, OC relapses in the majority of the cases. Several studies have suggested profound antitumor activity of cold atmospheric plasma (CAP). CAP is an ionized gas that mainly mediates its effects via the release of a variety of reactive oxygen and nitrogen species. Evidence of CAP treatment on OC cells is scarce, and accordingly we investigated their biological responses following exposure to plasma. Materials and Methods We tested the activity of CAP and CAP-treated medium to inactivate OC cell lines, and investigated their secretory products following CAP treatment. Cell proliferation and cell motility was measured. The presence of HSP27 was measured by Western blotting and enzyme-linked immunosorbent assay (ELISA). Supernatants of plasma-treated OC cells were added to the human THP-1 monocytic cell line. Cellular oxidation, viability, growth, morphology, surface marker expression, and cytokine release were monitored over up to 4 days of culture with supernatants of untreated and plasma-treated cancer cells. Results CAP treatment led to an attenuation of OC cell growth and motility. Incubation with CAP-treated cell culture medium gave similar effects. Results were consistent in four OC cell lines. Notably, CAP treatment of OC cells led to a decrease of intracellular HSP27 accompanied by an increase of extracellular HSP27 in the cell culture supernatant. These supernatants did not cause oxidation or blunted cell growth in THP-1 monocytes. Cell morphology was rather unaffected whereas from 12 cell surface markers screened, two (CD271 and CD55) gave a significant increase in plasma-treated OC cell supernatants compared to untreated controls. HSP27 alone led to a decrease of both markers. Likewise, a screening of 13 cytokines release from THP-1 revealed a differential regulation of a number of targets, for example, an upregulation of interleukin 8 in plasma-treated samples compared to untreated controls. Conclusion Plasma treatment was cytotoxic in ovarian cancer cell lines with functional and phenotypical consequences in human monocytes. The role of extracellular HSP27 induced by CAP treatment may represent immunomodulating mechanisms, which will be characterized more detailed in future.