Akademik Veri Yönetim Sistemi
Toxicology Letters, cilt.412, ss.162-171, 2025 (SCI-Expanded)
Abemaciclib is a cyclin-dependent kinase (CDK) enzyme inhibitor approved by the FDA for advanced and metastatic breast cancer therapy. Abemaciclib has caused someadverse reactions, such as dermatitis and skin reactions; however, the underlying cellular mechanism is still not obvious. In the current study, human keratinocyte HaCaT cells were treated with 0–10 µM abemaciclib for 24 h. The cytotoxic, apoptosis/necrosis, oxidative stress, and inflammation-inducing potentials of abemaciclib were evaluated. Abemaciclib induced cytotoxicity and the half-maximal inhibitory concentration (IC50) was computed to be ≥ 24.18 µM. It significantly induced apoptosis and oxidative damage in the lowest treatment group (0.1 µM). The time-dependent effects show that the highest effects were seen after 24 h. The study on low concentrations indicated that the maximum effects were seen in the 0.1 µM treatment group. There was a notable rise in the secretion of MCP-1, IL-6, and IL-8 at 0.1 µM, while it decreased at 1–10 µM. Similarly, the levels of other mediators were increased solely at 0.1 µM; however, no changes in the higher concentrations. The increase in TNF-α was significant at 5 µM; however, the increase diminished at the highest treatment concentration. It could be concluded that abemaciclib-induced toxicity could be via oxidative inflammation leading to cell death in human keratinocytes. No effect was detected in the higher concentrations, while the effect was observed in the lowest treatment group. These findings underscore the need for further comprehensive studies of the spectrum of activity and risk profile of abemaciclib and encourage future research in this area.