Vanadium compounds and cellular death mechanisms in the A549 cell line: The relevance of the compound valence.

Non‐small lung cell carcinoma has a high morbidity and mortality rates. The elective treatment for stage III and IV is cisplatinum that conveys serious toxic side effects. Vanadium compounds are metal molecules with proven antitumor activity that depends on its valence. Therefore, a better understanding of the mechanism of action of vanadium compounds is required. The aim of our study was to investigate the mechanisms of cell death induced by sodium metavanadate (NaVO3 [V(+5)]) and vanadyl sulfate (VOSO4 [(+4)]), both of which have reported apoptotic‐inducing activity. We exposed the A549 cell line to various concentrations (0‐100 μM) and to different exposure times to each compound and determined the cell viability and expression of caspases, reactive oxygen species (ROS) production, Bcl2, Bax, FasL and NO. Our results showed that neither compounds modified the basal expression of caspases or pro‐ and anti‐apoptotic proteins. The only change observed was the 12‐ and 14‐fold significant increase in ROS production induced by NaVO3 and VOSO4, respectively, at 100 μm concentrations after 48 hours. Our results suggest that classical apoptotic mechanisms are not related to the cell death induced by the vanadium compounds evaluated here, and showed that the higher ROS production was induced by the [(+4)] valence compound. It is possible that the difference will be secondary to its higher oxidative status and thus higher ROS production, which leads to higher cell damage. In conclusion, our results suggest that the efficacy of the cell death mechanisms induced by vanadium compounds differ depending on the valence of the compound. Lung cancer has a high mortality rate. In advanced stages, chemotherapy is the chosen treatment; however, toxic side effects are still a problem. Development of new molecules, which could overcome these disadvantages, should be a priority. Some metal compounds with proven antitumor activity, such as vanadium compounds, have been proven to inhibit the growth of cancer cells in vitro and in vivo assays. Therefore, a better understanding of the mechanism of action of vanadium compounds is required. [ABSTRACT FROM AUTHOR]