Cell lines

The human breast carcinoma cell lines (MCF-7 and MDA-MB-231)

Preparation method

The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0.1–100 μM for 72 hours.

Applications

Treatment of MCF-7 cells with a range of zoledronic acid concentrations had little effect on apoptosis at 0.1 and 1.0 μM, however, an increase in the proportion of apoptotic cells was observed with 10 μM and 100 μM zoledronic acid compared with control (28.7% and 70.7% vs 22.57%, respectively).Treatment of MDA-MB-231 cells with 0.1–1 μM zoledronic acid did not cause an increase in apoptosis, but treatment with the 10 and 100 μM zoledronic acid resulted in a significant increase in the proportions of apoptotic cells (126.6% and 126.6% of control). A significant time-dependent increase in MCF7 cell apoptosis was confirmed when cells were incubated with 100 μM zoledronic acid for 24–96 hours.

Animal models

The 5T2MM murine model (Male, 6-week-old, C57BL/KaLwRijHsd mice)

Dosage form

120 g/kg, subcutaneously (sc), twice weekly, 12 weeks.

Application

Treatment of mice bearing 5T2MM cells with zoledronic acid clearly prevented the development of osteolytic bone disease, decreased tumor burden in bone, and increased survival in a model of established myeloma.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Zoledronic Acid is a third-generation, nitrogen-containing bisphosphonate, inhibits osteoclast-mediated bone resorption, and also has antitumor activity.

Zoledronic Acid induces apoptosis in HGF and HaCaT cells at 0.5 μM, and causes cell death at 1-5 μM[1]. Zoledronic Acid (50, 100 μM) causes dose- and time-dependent apoptosis in CNE-2Z cells after treatment for 24, 48, and 72 h. Zoledronic Acid (50 μM) also increases the level of ROS, which is supposed to mediate Cl- currents activation in CNE-2Z cells. Furthermore, the apoptosis and chloride currents induced by Zoledronic Acid can be blocked by knocking down ClC-3 protein expression[2].

References:
[1]. Scheper M, et al. A novel soft-tissue in vitro model for bisphosphonate-associated osteonecrosis. ibrogenesis Tissue Repair. 2010 Apr 1;3:6.
[2]. Wang L, et al. The apoptotic effect of Zoledronic acid on the nasopharyngeal carcinoma cells via ROS mediated chloride channel activation. Clin Exp Pharmacol Physiol. 2018 Jun 8.