Overexpression of ZAKβ in human osteosarcoma cells enhances ZAKα expression, resulting in a synergistic apoptotic effect

Abstract

ZAK is a mixed lineage kinase involved in cell differentiation, proliferation, and hypertrophic growth. ZAKα isoform of ZAK is associated with tumorigenesis, but the function of ZAKβ is not yet known. In H9c2 cells, ZAKβ was found to ameliorate the apoptotic effect induced by ZAKα. However, in osteosarcoma cells, ZAKβ elevates the apoptotic effect induced by ZAKα. In this study, we show that similar to ZAKα, the ZAKβ induces apoptosis and decreases cell viability. Interestingly, the expression of ZAKβ is dependent on ZAKα expression, and ZAKβ further enhances ZAKα expression and results in synergistic enhancement of apoptosis in osteosarcoma cells.

Selective Activation of ZAK β Expression by 3-Hydroxy-2-Phenylchromone Inhibits Human Osteosarcoma Cells and Triggers Apoptosis via JNK Activation

“…ZAKβ can also activate JNK in response to saturated free fatty acids (FFA) [15]. In human OS cells, we found that ZAKβ could enhance ZAKα expression, resulting in a synergistic apoptotic effect [5,16]. In this study, we demonstrate that 3-HF can induce ZAK overexpression to trigger human OS cells apoptosis, and ZAKβ can play a leading role in activating ZAKα and a synergistic apoptotic effect.…”

“…In our previous publication, we demonstrated that doxorubicin can induce cell apoptosis by overexpression of ZAK in human OS cells [5]. Furthermore, we have also demonstrated that ZAKβ can enhance ZAKα expression in human OS cells, resulting in a synergistic apoptotic effect [16]. However, due to the adverse side effects associated with doxorubicin, various alternative drugs are under consideration [25,26].…”