Hanne Verswyvel

Chapter 5 │ Page 185 neighboring cells the damaging e ects of oxidative stress induced by α-particles [158]. Inhibition of GJs or downregulation of Cx43 proteins protected the cells against the toxic e ects, suggesting that GJs contribute to propagate radiation-induced cell death [158]. Therefore, designing strategies to increase GJs in cancer cells could improve the extension of cell death to neighboring cells, enhancing the e iciency of PDT or any other treatment based on oxidative stress, such as irradiation and NTP. Overall, oxidative stress has a crucial e ect on the function of GJs by inducing connexon opening to allow the entrance of RONS to cause cell injury and death. Afterwards, the use of inhibitors/blockers of connexons opening can increase the accumulation of intracellular RONS during oxidative stress, to enhance cell damage. To summarize, the oxidative damage caused by RONS on GJs can be used as a therapeutic strategy to induce cancer cell death, but their e ects are dependent on the treatment type and may vary among di erent cancer types. A promising therapeutic strategy based on oxidative stress to overcome the resistance of various cancer types to traditional treatments such as radiotherapy, chemotherapy, and surgery[159] is NTP, a promising therapeutic strategy being explored as a cancer (immuno-)therapy. NTP is a partially ionized gas composed of neutral gas molecules, positive and negative ions, free electrons, excited species and radicals. Of major importance for biomedical applications, including cancer therapy, is the multitude of short-lived and persistent RONS generated by NTP [36]. The observed anti-cancer e ects of these RONS have been attributed to the therapeutic response of NTP on cancer cells [160], with a particular emphasis on the short-lived species (e.g. HO●, O2 ●−, ●NO) [161]. Despite advances in understanding the e ect of RONS on GJs, some relevant questions pertaining to NTP treatment e ect remain open. For instance: 1) How can RONS be transported through GJs? 2) Can RONS chemically react with amino

RkJQdWJsaXNoZXIy MTk4NDMw