Objective:

2

To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells.

Methods:

2

Breast cancer 4T1 cells were divided into 6 groups: control

brazilin 1/2 half maximal inhibitory concentration (IC

50

)

IC

50

2×IC

50

erastin (10 μg/mL) and capecitabine (10 μg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay

and the treatment dose of brazilin was screened. The effect of brazilin on the m

itochondrial morphology of 4T1 cells

and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe

2+

reactive oxygen species (ROS)

malondialdehyde (MDA)

glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53

solute carrier family 7 member 11 (SLC7A11)

GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay.

Results:

2

Compared to the control group

the 10 (1/2 IC

50

)

20 (IC

50

) and 40 (2×IC

50

) μg/mL brazilin

erastin

and capecitabine groups showed a significant decrease in the cell survival rate

invasion and migration abilities

GSH

SLC7A11 and GPX4 protein expression levels

and mitochondrial volume and ridge (

P

<

0.05)

and a significant increase in the mitochondria membrane density

Fe

2+

ROS and MDA levels

and p53 and ACSL4 protein expression levels (

P

<

0.05).

Conclusions:

2

Brazilin actuated ferroptosis in breast cancer cells

and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.