Abstract
Background: YK-4-279, a promising anticancer agent, has demonstrated therapeutic potential against various tumors. Osteosarcoma (OS), an aggressive bone cancer primarily affecting adolescents, lacks effective treatment options. Investigating YK-4-279's mechanisms in OS is critical for evaluating its clinical utility. Methods: Using in vitro models, we examined YK-4-279's effects on OS cell viability, proliferation, apoptosis, cell cycle progression, and DNA damage. We also assessed its impact on MAPK signaling pathway activation. To clarify the pathway's role, we combined YK-4-279 treatment with a P38 inhibitor. Results: YK-4-279 markedly suppressed OS cell viability and proliferation, triggered G2/M phase arrest, and enhanced apoptosis and DNA damage. Furthermore, it activated the MAPK pathway, elevating phosphorylation of ERK1/2, JNK, and P38 MAPK. Co-treatment with a P38 inhibitor partially reversed these effects, confirming MAPK's involvement in YK-4-279's antitumor action. Conclusion: YK-4-279 inhibits OS cell growth, induces DNA damage and cell cycle arrest, and promotes apoptosis via MAPK pathway activation. These findings highlight its strong therapeutic potential for OS treatment.