Saffron carotenoids change the superoxide dismutase activity in breast cancer: In vitro, in vivo and in silico studies.

Superoxide dismutase (SOD) is an important member of the antioxidant defense system and is proposed as a therapeutic agent against the ROS-mediated diseases, and a therapeutic target for cancer treatment. Saffron carotenoids, crocin (Cro) and crocetin (Crt), are antioxidants with anticancer activity. In the present study, we investigated the effects of Cro/Crt on the SOD activity in both in vivo and in vitro models of breast cancer. Both Cro and Crt showed strong radical scavenging activity and SOD inhibition in the MCF-7 breast cancer cell line. The UV-Vis, circular dichroism and fluorometry studies proposed the binding of both Cro and Crt with SOD; the ΔG° of binding at 310 K was -8.6 and -4.4 kcal/mol, respectively. The docking analysis predicted the Cro/Crt binding near the active site channel, but in different sites. According to the obtained data, Cro inhibits SOD activity by scavenging superoxide radical (O₂), while Crt inhibits SOD by affecting the copper-binding site. In contrast to the in vitro data, both Cro and Crt effectively increased SOD activity in breast tumors of BALB/c mice, after one month of treatment. The mechanism that is important to compensate for the SOD decreased activity in cancer.