Biphasic effects of l-ascorbate on the tumoricidal activity of non-thermal plasma against malignant mesothelioma cells

Arch Biochem Biophys. 2016 Sep 1;605:109-16. doi: 10.1016/ Epub 2016 May 24.


Non-thermal plasma (NTP) is a recently developed technology that elicits a variety of biological effects. This includes cancer cell-specific cytotoxicity, which is mainly attributed to the regional generation of reactive oxygen species (ROS). We studied the effects of NTP on malignant mesothelioma (MM) and its modulation by l-ascorbate. l-ascorbate is a major water-soluble anti-oxidant in vivo, but its pro-oxidant activity in vitro has been well recognized. Thus, the effects of ascorbate on the efficacy of NTP is important to examine. NTP exposure dose-dependently killed MM cells, whereas MM cells tolerated 1 mM l-ascorbate. However, brief pre-treatment with a pharmacological dose (250-750 μM) of l-ascorbate immediately prior to NTP exposure significantly increased its cytotoxicity in a dose-dependent manner, which was inhibited by the iron chelator, deferoxamine. However, paradoxically, this potentiating effect of l-ascorbate was completely abolished by a prolonged 4 h pre-incubation with l-ascorbate (500 μM). MM cytotoxicity induced by NTP was associated with immediate oxidative stress evaluated by 2',7'-dichlorodihydrofluorecein diacetate, which was followed by an increase in the expression of the autophagosome marker, LC3B-II. In conclusion, MM can be a target for NTP treatment and l-ascorbate can increase or decrease its efficacy depending on the length of the pre-incubation period.

Keywords: Autophagy; Mesothelioma; Non-thermal plasma (NTP); Reactive oxygen species (ROS); l-ascorbate.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antioxidants / chemistry
  • Apoptosis
  • Ascorbic Acid / chemistry*
  • Autophagy
  • Cell Line, Tumor
  • Cell Survival
  • Deferoxamine / chemistry
  • Dose-Response Relationship, Drug
  • Humans
  • Lung Neoplasms / drug therapy*
  • Mesothelioma / drug therapy*
  • Mesothelioma, Malignant
  • Microscopy, Fluorescence
  • Oxidative Stress
  • Plasma Gases*
  • Reactive Oxygen Species / chemistry
  • Temperature


  • Antineoplastic Agents
  • Antioxidants
  • Plasma Gases
  • Reactive Oxygen Species
  • Deferoxamine
  • Ascorbic Acid