Induction of apoptosis using ATN as a novel Yes-associated protein inhibitor in human oral squamous cell carcinoma cells
Chu, Po Chen; Dokla, Eman; Hu, Jing Lan; Weng, Jing Ru;
Abstract
Oral squamous cell carcinoma (OSCC) represents a clinical challenge due to the lack of effective therapy to improve prognosis. Hippo/Yes-associated protein (YAP) signaling has emerged as a promising therapeutic target for squamous cell carcinoma treatment. In this study, we investigated the antitumor activity and underlying mechanisms of {[N-(4-(5-(3-(3-(4-acetamido-3-(trifluoromethyl)phenyl)ureido)phenyl)-1,2,4-oxadiazol-3-yl)-3-chlorophenyl)-nicotinamide]} (ATN), a novel YAP inhibitor, in OSCC cells. ATN exhibited differential antiproliferative efficacy against OSCC cells (IC50 as low as 0.29 μM) versus nontumorigenic human fibroblast cells (IC50 = 1.9 μM). Moreover, ATN effectively suppressed the expression of YAP and YAP-related or downstream targets, including Akt, p-AMPK, c-Myc, and cyclin D1, which paralleled the antiproliferative efficacy of ATN. Supporting the roles of YAP in regulating cancer cell survival and migration, ATN not only induced caspase-dependent apoptosis, but also suppressed migration activity in OSCC. Mechanistically, the antitumor activity of ATN in OSCC was attributed, in part, to its ability to regulate Mcl-1 expression. Together, these findings suggest a translational potential of YAP inhibitors, represented by ATN as anticancer therapy for OSCC.
Other data
Title | Induction of apoptosis using ATN as a novel Yes-associated protein inhibitor in human oral squamous cell carcinoma cells | Authors | Chu, Po Chen; Dokla, Eman ; Hu, Jing Lan; Weng, Jing Ru | Keywords | apoptosis | Mcl-1 | migration | OSCC | YAP | Issue Date | 1-Jun-2022 | Publisher | WILEY | Journal | Environmental Toxicology | ISSN | 15204081 | DOI | 10.1002/tox.23493 | PubMed ID | 35212453 | Scopus ID | 2-s2.0-85125173631 | Web of science ID | WOS:000760875700001 |
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