Oxaliplatin induces the PARP1-mediated parthanatos in oral squamous cell carcinoma by increasing production of ROS.
Aging (Albany NY)
; 13(3): 4242-4257, 2021 01 20.
Article
in En
| MEDLINE
| ID: mdl-33495407
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mouth Neoplasms
/
Reactive Oxygen Species
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Poly (ADP-Ribose) Polymerase-1
/
Oxaliplatin
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Squamous Cell Carcinoma of Head and Neck
/
Parthanatos
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Mitochondria
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Aging (Albany NY)
Journal subject:
GERIATRIA
Year:
2021
Document type:
Article
Affiliation country:
China
Country of publication:
United States