Biodegradable magnesium alloys are promising materials for osteosynthesis. We claim that they also be used for therapeutic purposes, particularlyin cancer patients after resection of primary tumors and bone metastases.This can be achieved by alloying Mg alloys with rare earth (RE) elements, which are known to have a cytotoxic effect on tumor cells.This may allow control of residual disease in cancer patients after radical and conditional-radical surgery.
With this idea in mind, we analyzed the apoptotic reaction of MCF7 (human breast adenocarcinoma cell line) and LnCap (human prostate adenocarcinoma cells line) cells in response to coincubation with samples based on a Mg alloy containing RE elements in a homogenized condition and after severe plastic deformation by equal channel angular pressing (ECAP). This processing leads to extreme grain refinement and ensuing improvement of mechanical strength of the alloy. We investigated the influence of the alloy with RE elements on the viability, cell cycle and apoptosis, nitric oxide (NO) activity and oxidative stress with detection of reactive oxygen species (ROS) in cancer cells. Our results demonstrated that even short-term culturing of cells with the alloy specimens induce expression of NO and caspase activity, DNA damage, and oxidative stress in cancer cells. In particular, after 2 hours of coincubation (37 °С, 5% CO2) with homogenized and ECAP-processed samples the concentration of ROS+ cells dropped by 11±5.2% and 13±3.1% in MCF7 culture and by 5±2.8% and 6±2.8% in LnCap culture, respectively. Fluctuations in NO+ cell concentrations were small: after coincubation with the homogenized alloy the concentration of NO+ live cells in both cultures was increased by1.6-2.8%, and with the ECAP one the concentration of NO+ dead cells rose by 0.9-1%. These distinct signs of apoptosis were accompanied with a decrease in cell viability: after coincubation with the alloy in both conditions viability of MCF7 decreased by 8±1.2% and 7±2.2%; and that of LnCap by 10±0.1% and 2±0.5%, respectively.
Our work confirms the occurrence of antitumor activity of magnesium alloy with RE expressed through apoptosis of cancer cells. The results obtained give promise for the development of Mg based implants for reconstructive surgery for tumor recurrence and metastasis prevention in cancer patients.
Funding for this research provided by the Russian Science Foundation (grant #18-45-06010) is gratefully acknowledged.