Open AccessAripiprazole sensitizes head and neck cancer cells to ionizing radiation by enhancing the production of reactive oxygen species
Author(s) -
Jeong HyeonJeong,
Jung ChanWoong,
Kim HeeJin,
Park Byunghee,
Moon Youna,
Kim JeongYub,
Park MyungJin
Publication year - 2022
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.989
Subject(s) - aripiprazole , reactive oxygen species , pharmacology , chemistry , apoptosis , radiosensitizer , in vivo , propidium iodide , head and neck cancer , medicine , cancer , cancer research , programmed cell death , radiation therapy , biology , biochemistry , schizophrenia (object oriented programming) , microbiology and biotechnology , psychiatry
Drug repositioning is an alternative process for drug development in cancer. Specifically, it is a strategy for the discovery of new antitumor drugs by screening previously approved clinical drugs. On the basis of this strategy, aripiprazole, an antipsychotic drug, was found to have anticancer activity. In this study, we investigated the radiosensitizing effects of aripiprazole on head and neck cancer cells at sublethal doses of ionizing radiation (IR) in vitro and in vivo. Treatment with aripiprazole suppressed the growth of head and neck cancer cells in a concentration‐dependent manner, as evidenced by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Intriguingly, aripiprazole significantly enhanced the sensitivity of these cells to the IC 50 dose of IR. The combination of aripiprazole with IR synergistically increased annexin and propidium iodide double‐positive and terminal deoxynucleotidyl transferase dUTP nick end labeling‐positive cell populations, and induced cleaved poly(ADP‐ribose) polymerase and caspase‐3 expression, indicating the induction of apoptosis in these cells. Aripiprazole and IR‐induced apoptosis were accompanied by an increase in reactive oxygen species and was almost completely suppressed by the addition of the antioxidant, N‐acetylcysteine. Finally, aripiprazole greatly sensitized xenograft tumors to IR at doses that did not affect tumor growth. Taken together, these results suggest that aripiprazole could be considered a potent radiosensitizer for head and neck cancer.