Oxidative Stress Pathways Linked to Apoptosis Induction by Low-Temperature Plasma Jet Activated Media in Bladder Cancer Cells: An In Vitro and In Vivo Study
Hideo Fukuhara,
Endre J. Szili,
Jun-Seok Oh,
Kawada Chiaki,
Shinkuro Yamamoto,
Atsushi Kurabayashi,
Mutsuo Furihata,
Masayuki Tsuda,
Hiroshi Furuta,
Howard D. Lindsay,
Robert D. Short,
Akimitsu Hatta,
Keiji Inoue
Affiliations
Hideo Fukuhara
Department of Urology, Kochi Medical School, Nankoku 783-8505, Japan
Endre J. Szili
Future Industries Institute, Adelaide, SA 5095, Australia
Jun-Seok Oh
Department of Physics and Electronics, Graduate School of Engineering, Osaka Metropolitan University, Osaka 558-8585, Japan
Kawada Chiaki
Department of Urology, Kochi Medical School, Nankoku 783-8505, Japan
Shinkuro Yamamoto
Department of Urology, Kochi Medical School, Nankoku 783-8505, Japan
Atsushi Kurabayashi
Department of Pathology, Kochi Medical School, Nankoku 783-8505, Japan
Mutsuo Furihata
Department of Pathology, Kochi Medical School, Nankoku 783-8505, Japan
Masayuki Tsuda
Division of Laboratory Animal Science, Life Sciences and Functional Materials Section, Kochi Medical School, Nankoku 783-8505, Japan
Hiroshi Furuta
Department of Electronic & Photonic Systems Engineering, Kochi University of Technology, Kami 782-8502, Japan
Howard D. Lindsay
Lancaster Medical School, Lancaster University, Lancaster LA1 4YW, UK
Robert D. Short
Department of Chemistry and Material Science Institute, Lancaster University, Lancaster LA1 4YW, UK
Akimitsu Hatta
Department of Electronic & Photonic Systems Engineering, Kochi University of Technology, Kami 782-8502, Japan
Keiji Inoue
Department of Urology, Kochi Medical School, Nankoku 783-8505, Japan
Current methods used to treat non-muscle invasive bladder cancer are inadequate due to a high recurrence rate after surgery and the occurrence of adverse events such as interstitial pneumonia following intravesical instillation therapy. Low-temperature plasma is a new form of physical therapy that provides a rich source of reactive oxygen species (ROS). Oxidative solutions, created by pre-treatment of aqueous media with plasma before application to target cells, lead to the destruction of cancer cells through oxidative stress pathways. This study focuses on the effects of plasma-activated media (PAM) in bladder cancer cells. PAM treatment increases oxidative stress that leads to cell cycle arrest and concomitantly depolarises the mitochondrial membrane leading to increased mitochondrial ROS production. Cell cycle arrest and increased mitochondrial ROS production led to an increase in caspase 3/cytochrome c activity, which might explain the induction of apoptosis in bladder cancer cells in vitro and in a bladder cancer tumour in vivo. These observations highlight the potential of plasma activated solutions as a new adjuvant therapy in the clinical treatment of bladder cancer.
