Assessment of the Therapeutic Effects of Zoledronic Acid on Breast Cancer Subtypes

Objective: Breast cancer is a heterogeneous type of cancer with many subtypes and is the most common cancer among women. It is noteworthy that breast cancer subtype-based treatment options have attracted great attention. In the present study, we aimed to investigate the therapeutic effect of a bisphosphonate inhibitor zoledronic acid (ZOL), which is a clinically used in the treatment of cancer types with bone metastases and has been found to exert anti-proliferative and anti-metastatic effects, on two different subtypes of breast cancer [MCF-7 (ER+, PR+, HER2-) and MDA-MB-231 (ER-, PR-, HER2-)] and HUVEC control cells. Materials and Methods: The cytotoxic and apoptotic effect of ZOL (10-100 uM) for 24 and 48 hours was determined by WST-1, Annexin V and cell cycle analysis. In addition, changes in cell morphology and nucleus after treatment with ZOL observed by acridine orange (AO) and DAPI staining, respectively. Results: ZOL caused more anti-proliferative effect and early and late apoptotic death in MDA-MB-231 cells compared with MCF-7 cells (p<0.05). The cell population in G0/G1 phase was significantly increased after treatment with especially 50 and 100 μM ZOL (p <0.05). Additionally, the loss of cell membrane integrity and chromatin condensation were observed in MCF-7 and MDA-MB-231 cells treated with ZOL. However, ZOL had a toxic effect on HUVEC cells at higher concentrations. Conclusion: In conclusion, although ZOL has a potential therapeutic effect on different subtypes of breast cancer, ZOL causes more cytotoxic effects and apoptotic death in triple negative breast cancer (MDA-MB-231) cells than hormone sensitive (MCF-7) cells. However, further studies are needed to determine the molecular mechanisms underlying the therapeutic effect of ZOL depending on subtypes of breast cancer and the optimal schedule and dose of ZOL