Non-Thermal Plasma Couples Oxidative Stress to TRAIL Sensitization through DR5 Upregulation

International Journal of Molecular Sciences

Youngsoo Lee¹  TaeJung Kim²  SoonYoung Hwang³  Jong-Soo Lee³  NgocHoan Nguyen³  MiAe Kang³ 

[1] Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea;Department of Electrical and Computer Engineering, College of Information and Technology, Ajou University, Suwon 16499, Korea;Department of Life Sciences, College of Natural Sciences, Ajou University, Suwon 16499, Korea;

关键词: plasma-activated medium;    TRAIL;    DR5;    apoptosis;    ROS/RNS;   

DOI  :  10.3390/ijms21155302

来源: DOAJ

【 摘 要 】

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells without affecting most normal cells. Despite being in clinical testing, novel strategies to induce TRAIL-mediated apoptosis are in need to overcome cancer cell unresponsiveness and resistance. Plasma-activated medium (PAM) markedly stimulates reactive oxygen/nitrogen species (ROS/RNS)-dependent apoptosis in cancer cells. We investigate the capability of PAM and TRAIL (PAM/TRAIL) combination therapy to overcome TRAIL resistance and improve the anticancer efficacy of TRAIL. The combinatorial treatment of PAM and TRAIL shows synergistic effects on growth inhibition in TRAIL-resistant cancer cells via augmented apoptosis by two attributes. DR5 (TRAIL-R2) transcription by CHOP is upregulated in a PAM-generated ROS/RNS-dependent manner, and PAM itself upregulates PTEN expression mediated by suppression of miR-425 which is involved in Akt inactivation, leading to increased apoptosis induction. Treatment of cancer cell lines with the antioxidant N-acetylcysteine reduces the extent of membrane dysfunction and the expression of both CHOP-DR5 and miR-425-PTEN axes, attenuating PAM/TRAIL-induced cancer cell apoptosis. These data suggest that PAM/TRAIL treatment is a novel approach to sensitizing cancer cells to TRAIL-induced apoptosis and overcoming TRAIL resistance. PAM is a promising candidate for further investigations as a chemotherapeutic sensitizer in the treatment of cancer.

【 授权许可】

Unknown