RT Journal Article
SR Electronic
T1 Reactivation of p53 by RITA Induces Apoptosis in Human Oral Squamous Cell Carcinoma Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2931
OP 2937
DO 10.21873/anticanres.15775
VO 42
IS 6
A1 MANABU ENDO
A1 TAKASHI NISHIOKA
A1 KENTO NUMAZAKI
A1 HIROSHI HASEGAWA
A1 TETSU TAKAHASHI
A1 SHUNJI SUGAWARA
A1 HIROYUKI TADA
YR 2022
UL http://ar.iiarjournals.org/content/42/6/2931.abstract
AB Background/Aim: Oral squamous cell carcinoma (OSCC) is one of the most common tumors of the head and neck region. The tumor suppressor gene p53 (TP53) is the most frequently mutated gene in OSCC and TP53 mutations are associated with decreased survival and resistance to chemotherapy in patients with OSCC. Therefore, therapeutic strategies targeting TP53 reactivation are required to effectively treat OSCC. In this study, we investigated the effect of various p53-reactivating small molecules (RITA, PRIMA-1, and CP-31398) on the proliferation of human OSCC cell lines (Ca9-22, HSC-2, HSC-3, and HSC-4) derived from human oral tissues bearing a mutant TP53 gene. Materials and Methods: Apoptosis induction by RITA was assessed by measuring Annexin V and propidium iodide (PI)-positive cells using flow cytometry. p53 and murine double minute 2 (MDM2) phosphorylation and Bax expression were detected in the lysates of RITA-treated Ca9-22 cells using western blotting. Results: RITA markedly inhibited the growth of Ca9-22, HSC-2, HSC-3, and HSC-4 cells. In Ca9-22 cells, RITA induced apoptosis and inhibited cell proliferation while increasing p53 phosphorylation and Bax expression; however, RITA did not induce MDM2 phosphorylation. Conclusion: The inhibitory effect of RITA on human OSCC cell proliferation is mediated by apoptosis induction through p53 and Bax.