TY  - JOUR
T1  - MAPK-Dependent Anticancer Effects of YK-4-279 in Osteosarcoma: Cell Cycle Arrest, DNA Damage, and Apoptosis
A1  - Lucas Meyer
A1  - Anna Schmid
A1  - Stefan Braun
JF  - Pharmaceutical Sciences and Drug Design
JO  - Pharm Sci Drug Des
SN  - 3062-4428
Y1  - 2026
VL  - 6
IS  - 1
DO  - 10.51847/ZyReFZZLfR
SP  - 39
EP  - 56
N2  - YK-4-279 is an emerging anticancer compound that has demonstrated activity across a range of tumor models. Osteosarcoma (OS), a highly aggressive bone malignancy predominantly diagnosed in adolescents, still lacks satisfactory therapeutic options. A detailed investigation of how YK-4-279 functions in OS is essential for determining its potential clinical relevance. Therefore, the present study aimed to evaluate its effects on OS cell viability, proliferation, DNA damage, cell cycle regulation, apoptosis, and MAPK signaling activity, potentially providing a novel basis for osteosarcoma treatment and prognosis. In vitro experimental systems were used to evaluate the effects of YK-4-279 on osteosarcoma cell viability, proliferation, programmed cell death, cell cycle distribution, and DNA damage responses. Its regulatory influence on MAPK signaling activity was also analyzed. To further verify pathway involvement, cells were treated with YK-4-279 in combination with a P38-specific inhibitor. Treatment with YK-4-279 significantly impaired osteosarcoma cell survival and proliferation, induced arrest at the G2/M checkpoint, and increased both apoptotic activity and DNA damage levels. In parallel, MAPK signaling was activated, as indicated by enhanced phosphorylation of ERK1/2, JNK, and P38 MAPK. Notably, inhibition of P38 partially mitigated these effects, supporting a functional role for MAPK signaling in mediating the compound’s anticancer activity. YK-4-279 exerts strong inhibitory effects on osteosarcoma cell growth by promoting DNA damage, enforcing cell cycle arrest, and activating apoptosis through MAPK pathway stimulation. These findings suggest its potential as a promising candidate for osteosarcoma therapy.
UR  - https://galaxypub.co/article/mapk-dependent-anticancer-effects-of-yk-4-279-in-osteosarcoma-cell-cycle-arrest-dna-damage-and-ap-jy7rq7qh0c4ielv
ER  -