posted on 2023-01-06, 19:04authored byYuxiang Zhao, Yabei Li, Shuake Kuermanbayi, Yulin Liu, Junjie Zhang, Zhaoyang Ye, Hui Guo, Kai Qu, Feng Xu, Fei Li
Ferroptosis, as a promising therapeutic strategy for
cancers, has
aroused great interest. Quantifying the quick dynamic changes in key
parameters during the early course of ferroptosis can provide insights
for understanding the underlying mechanisms of ferroptosis and help
the development of therapies targeting ferroptosis. However, in situ
and quantitatively monitoring the quick responses of living cancer
cells to ferroptosis at the single-cell level remains technically
challenging. In this work, we selected HuH7 cells (hepatocellular
carcinoma (HCC) cells) as a cell model and Erastin as a typical ferroptosis
inducer. We utilized scanning electrochemical microscopy (SECM) to
quantitatively and in situ monitor the early course of ferroptosis
in HuH7 cells by characterizing the three key parameters of cell ferroptosis
(i.e., cell membrane permeability, respiratory activity, and the redox
state). The SECM results show that the membrane permeability of ferroptotic
HuH7 cells continuously increased from 0 to 8.1 × 10–5 m s–1, the cellular oxygen consumption was continuously
reduced by half, and H2O2 released from the
cells exhibited periodic bursts during the early course of ferroptosis,
indicating the gradually destroyed cell membrane structure and intensified
oxidative stress. Our work realizes, for the first time, the in situ
and quantitative monitoring of the cell membrane permeability, respiratory
activity, and H2O2 level of the early ferroptosis
process of a single living cancer cell with SECM, which can contribute
to the understanding of the physiological process and underlying mechanisms
of ferroptosis.