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. 2025;25(9):610-619.
doi: 10.2174/0118715206336754241015062614.

Synergistic Anti-tumorigenic Effects of Cabazitaxel and Usnic Acid Combination on Metastatic Castration-Resistant Prostate Cancer Cells

Ceyda Colakoglu Bergel  1 , Isil Ezgi Eryilmaz  1 , Ebrucan Bulut  1 , Rumeysa Fatma Balaban  1 , Unal Egeli  1 , Gulsah Cecener  1
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Synergistic Anti-tumorigenic Effects of Cabazitaxel and Usnic Acid Combination on Metastatic Castration-Resistant Prostate Cancer Cells

Ceyda Colakoglu Bergel et al. Anticancer Agents Med Chem. 2025.

Abstract

Background: Prostate cancer (PC) affects millions of men, causing high mortality rates. Despite the treatment approaches, the options for metastatic castration-resistant prostate cancer (mCRPC), a lethal form of advanced PC, are still limited. Cabazitaxel (Cbx) is the last taxane-derived chemotherapeutic approved for Docetaxel- resistant mCRPC patients. However, its effects are limited due to the activation of several pathways. Therefore, new approaches are needed to increase the efficacy of Cbx. Usnic acid (UA) is a natural product with wellknown anti-tumorigenic and synergistic effects with various chemotherapeutics. Although the cytotoxicity of UA and Cbx has been evaluated on mCRPC cells, the anti-tumorigenic effect of UA combination with any taxane has not been investigated yet. Thus, we aimed to evaluate the possible synergistic effect of Cbx+UA in mCRPC cells.

Methods: Cell viability and apoptosis were analyzed using WST-1 and Annexin-V. Morphological changes were visualized by fluorescent staining. Finally, cell cycle, mitochondrial health, and ROS levels were determined.

Results: Based on WST-1 results, 25 μM UA exhibited significant additive and synergistic effects with the use of Cbx. Annexin V and cell cycle results showed that UA significantly enhanced the Cbx efficacy at increasing doses compared to using only Cbx (**p<0.01). Moreover, combined treatment significantly increased ROS levels and mitochondrial membrane depolarization compared with Cbx alone (**p<0.01).

Conclusions: Thus, the results suggest that UA increased the anti-tumorigenic effects of Cbx on mCRPC cells by increasing apoptosis, causing an increase in intracellular ROS and disrupting mitochondrial health. Consequently, combining UA and Cbx offers a new combined therapeutic strategy for mCRPC treatment.

Keywords: Cabazitaxel; cytotoxic effect; mCRPC treatment.; prostate cancer; synergistic effect; usnic acid.

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