Ferroptosis is involved in the anti-tumor effect of lycorine in renal cell carcinoma cells.

Abstract

Renal cell carcinoma (RCC) is a most common malignant tumor in the genitourinary system. Studies have shown that Lycorine has promising anticancer activities with minor side effects. However, the effect of lycorine on the proliferation of RCC cells and its underlying anti-tumor mechanism have not yet been fully elucidated. The human renal cancer cell lines 786-O, A498 and Caki-1 were cultured and treated with different concentrations of lycorine or ferrostatin-1, a ferroptosis inhibitor. Cell viability and colony formation assays were used to measure cell proliferation. The 5-, 12- and 15-HETE hydroxyeicosatetraenoic acid (HETE) and MDA levels, as well as the reduced to oxidized glutathione (GHS/GSSG) ratio, were analyzed. Western blot analysis was used to detect the expression of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long chain family member 4 (ACSL4), which are key markers of ferroptosis. Transmission electron microscopy was used to observe the morphological features associated with ferroptosis. Lycorine was found to inhibit the proliferation of RCC cells. After lycorine treatment, the expression levels of GPX4 in RCC cells decreased, whereas those of ACSL4 increased. Lycorine induced the expression of 5-HETE, 12-HETE, 15-HETE and MDA in RCC cells, and reduced the GSH/GSSG ratio. In addition, ferrostatin-1 could prevent lycorine-induced ferroptosis in RCC cells.