BULLFROG OIL (Rana catesbeiana SHAW) INDUCES APOPTOSIS IN HUMAN MELANOMA CELLS BY MITHOCONDRIAL DYSFUNCTION TRIGGERED BY OXIDATIVE STRESS
Bullfrog oil; Emulsion; Melanoma; Rana catesbeiana Shaw; Skin cancer.
Bullfrog oil (BO) is an animal oil obtained by the adipose tissue biotechnological reuse from the amphibious Rana catesbeiana Shaw and that has showed biocompatibility to healthy cells (3T3) and cytotoxicity against murine melanoma cells (B16F10). Based on this, and the currently necessity of new alternative treatments against skin cancer, this work aimed to reproduce an emulsified nanosystem (EN) containing BO and to evaluate its cytotoxic effect, for BO in natura and delivery by EN, against human melanoma cell line A2058. Then, in vitro assays, such as MTT assay, cell cycle analyze and cell death evaluation were performed to evaluate the cytotoxic effect. In addition, the apoptotic potential by DNA damage using iodide propidium staining analyze, determination of mitochondrial membrane potential and evaluation of oxidative stress and was also evaluated. The results showed that both BO and EN, at oil concentration at 100 ìg/mL were able to decrease the cell viability up to 40% and 80%, respectively, without to affect the cell cycle. Additionally, BO was able to induce the cell death by apoptosis, inducing the oxidative stress by increase up to 51% in the intracellular reactive oxygen species (ROS), leading to a mitochondrial membrane potential disruption. Additionally, the EN was also able to improve the BO cytotoxic effect, since promoted a significant oxidative stress, increasing in 178% the ROS level and, consequently, leading to a greater interference in the mitochondrial membrane potential. Thus, the obtained results allowed us to evaluate and elucidate the BO and EN cytotoxic effect, which were able to promote the human melanoma cell death by oxidative stress associated with mitochondrial damage, promoting the apoptosis induction, highlighting the cytotoxic potential of BO and EN as promising pharmaceutical products able to improve the alternative treatment arsenal against melanoma.