In Vitro Effects of Cabazitaxel and Menadione on Cell Growth, Metabolism, and Transcriptomic Profile of Human...

Cabazitaxel is a second-generation semisynthetic taxane approved for the treatment of prostate cancer. Vitamin K, an essential nutrient involved in blood coagulation and bone metabolism, has also been shown to have antineoplastic effects. However, no information is currently available regarding the combinatorial effects of cabazitaxel and menadione (VK3, a derivative of vitamin K) on prostate cancer cells. Therefore, we investigated the in vitro effects of cabazitaxel, VK3, and their combination on growth, mitochondrial bioenergetics, and glycolytic parameters using the human prostate cancer cell lines PC-3 and DU 145. All treatments inhibited the cell growth, but the combination of cabazitaxel and VK3 produced a synergistic effect that was stronger than either compound alone, and these effects were accompanied by cell line-specific bioenergetic changes and glycolytic responses. Furthermore, high-throughput transcriptomic profiling of PC-3 cells revealed distinct sets of differentially expressed genes for each treatment, with the greatest effect established by the combinatorial treatment, followed by VK3, and then cabazitaxel. Gene ontology analyses showed that the combinatorial treatment was associated with biological processes such as positive regulation of reactive oxygen species metabolic process, steroid metabolic process, proteolysis, and signal transduction. Notably, the treatments altered the gene expression of several tumorigenic and immunologic mediators, including MSXI, ZRSR2, GALNTL6, IL24, and IL18R1, which may impact cancer cell behavior. In conclusion, these in vitro findings indicate that the combination of cabazitaxel with VK3 is more effective in inhibiting prostate cancer cell growth than either agent alone and provide exploratory mechanistic insight into their effects on cancer cell metabolism and gene expression.