Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1

Abstract

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo , accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N -acetyl- l -cysteine, l -glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[ O -methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment.

The effect of a static magnetic field and baicalin or baicalein interactions on amelanotic melanoma cell cultures (C32)

“…Although the anticancer activity of baicalin may involve a pro-oxidant mechanism, these compounds also cause a depletion of the GSH content in human hepatoma cells [ 21 ]. Kong et al [ 22 ] investigated the effect of baicalin on the bladder cancer cells 5637 and KU-19-19 and found that baicalin performed its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Baicalin-induced ferroptotic cell death in vitro and in vivo, which is accompanied by an accumulation of reactive oxygen species (ROS) and the enrichment of intracellular chelate iron.…”

Frontiers of Ferroptosis in Cancer Treatment

“…A natural product baicalin was found to induce ferroptosis in bladder cancer cells 5637 and KU-19-19 by regulating ferritin heavy chain 1 (FTH1). Intraperitoneally injected Baicalin induced regression of the tumor mass in mice inoculated with KU-19-19 cells (90). Fin56 which is a type 3 ferroptosis inducer promotes GPX4 degradation and triggers ferroptosis in bladder cancer cells.…”

The Role Played by Ferroptosis in Osteoarthritis: Evidence Based on Iron Dyshomeostasis and Lipid Peroxidation

“…Feng et al [ 22 ] used an anti-3F3 ferroptotic membrane antibody (3F3-FMA) to detect ferroptotic cells, discovering that 3F3-FMA is a TfR1 antigen; hence, they concluded that TfR1 accumulation on the cell surface is a feature of ferroptosis. In researching baicalin-triggered ferroptosis in vitro and in vivo, Kong et al [ 23 ] found higher intracellular chelated iron levels after FTH1 overexpression in bladder cancer cells, indicating that baicalin-induced ferroptosis was accelerated by downregulating FTH1 expression. Bao et al [ 24 ] found ferroptosis phenotypes in the brains of Alzheimer’s disease (AD) model mice, and in these mice, ferroptosis was induced by downregulating FPN expression.…”