Research Paper Volume 13, Issue 3 pp 4242—4257
Oxaliplatin induces the PARP1-mediated parthanatos in oral squamous cell carcinoma by increasing production of ROS
- 1 Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China
- 2 Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
- 3 Life Science Institute of Jinzhou Medical University, College of Basic Medicine of Jinzhou Medical University, Cell Biology and Genetic Department of Jinzhou Medical University, Key Lab of Molecular and Cellular Biology of the Education Department of Liaoning Province, Jinzhou 121001, China
Received: August 17, 2020 Accepted: October 22, 2020 Published: January 20, 2021https://doi.org/10.18632/aging.202386
How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide, and its prognosis is still not optimistic. Oxaliplatin is a type of platinum chemotherapeutic agent, but its treatment effects on OSCC and molecular mechanisms have not been fully elucidated. Parthanatos, a unique form of cell death, plays an important role in a variety of physiological and pathological processes. This study aims to investigate whether oxaliplatin inhibits OSCC by inducing parthanatos. Our results showed that oxaliplatin inhibited the proliferation and migration of OSCC cells in vitro, and also inhibited the tumorigenesis in vivo. Further experiments proved that oxaliplatin induced parthanatos in OSCC cells, characterized by depolarization of the mitochondrial membrane potential, up-regulation of PARP1, AIF and MIF in the nucleus, as well as the nuclear translocation of AIF. Meanwhile, PARP1 inhibitor rucaparib and siRNA against PARP1 attenuated oxaliplatin-induced parthanatos in OSCC cells. In addition, we found that oxaliplatin caused oxidative stress in OSCC cells, and antioxidant NAC not only relieved oxaliplatin-induced overproduction of reactive oxygen species (ROS) but also reversed parthanatos caused by oxaliplatin. In conclusion, our results indicate that oxaliplatin inhibits OSCC by activating PARP1-mediated parthanatos through increasing the production of ROS.