Induction of apoptosis using ATN as a novel Yes‐associated protein inhibitor in human oral squamous cell carcinoma cells

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 mech-a novel YAP inhibitor, in OSCC cells. ATN exhibited differential antiproliferative efficacy against OSCC cells (IC 50 as low as 0.29 μM) versus nontumorigenic human fibroblast cells (IC 50 = 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 caspasedependent 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.

Discovery of the tryptanthrin‐derived indoloquinazoline as an anti‐breast cancer agent via ERK/JNK activation

“…Cells (2 × 10 5 ) were treated with CIQ in 6‐well plates for 48 h, then washed with ice‐cold PBS twice and harvested with trypsin. Cells were incubated with 5 μL Annexin V‐FITC/propidium iodide (PI) (BD Pharmingen, San Diego) for 15 min in the dark condiction 25 . Then, the cells were measured by BD FACSCanto flow cytometer (BD, Franklin Lakes, NJ).…”

“…Cells were incubated with 5 μL Annexin V-FITC/propidium iodide (PI) (BD Pharmingen, San Diego) for 15 min in the dark condiction. 25 Then, the cells were measured by BD FACSCanto flow cytometer (BD, Franklin Lakes, NJ). For caspase 3 activity, the commercial assay kit was purchased from BD Biosciences and evaluated according to…”