Page 23 - G. Cell differentiation. division. and death

Identification of natural compound inhibitors of ferroptosis
in cardiomyocytes

1,2
Jeong Eun Lee ,Kwang-Hee Bae , Sang Chul Lee , Eun-Woo Lee 1
1,2
1,2
1 Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon , Korea
2 Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Korea
BACKGROUND METHODS
Ferroptosis: cell death by lipid peroxidation Screening of the natural compound library
for inhibitors of ferroptosis

Myocardial infarction (MI) and ferroptosis

Flow chart of compound screen using cell viability assay and
AIM Experimental timeline of compound and RSL3 treatment. Briefly, H9c2
cells per well were pretreated with compounds for 30 min, and then
To identify natural compounds as novel ferroptosis inhibitor in treated with 3 μM RSL3. Cell viability was examined using CellTiter-Glo
cardiomyocytes and potential therapeutic agents against at 24 h treatment.
myocardial infarction (MI)
RESULTS

Several natural compounds significantly inhibited
RSL3-induced ferroptosis

Several compounds inhibited RSL3-induced cell death.
Compound 251 decreased ferroptosis induced by
12 compounds showed 70% of inhibition in comparison to control in cysteine and methionine deprivation
1 screening results, and 4 compounds displayed significant inhibition
st
against ferroptotic cell death comparable Fer-1 rescue in 2 nd screening
results.

Compound 251 decreased LDH and cell death
under cysteine and methionine deficiency conditions.
Compound 251 and 275 did not inhibit
H O -induced cell death
2
2
Several compounds reduced RSL3-induced lipid peroxidation and LDH.

Compound 251 inhibited ferroptosis,
but did not reduced early lipid ROS induced by RSL3 Compound 251 and 275 might not be general antioxidant.
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

 4 candidate compounds significantly Behrouz H. et al. (2019) Targeting This research was supported by a grant
inhibited RSL3-induced ferroptosis in ferroptosis to iron out cancer. Cancer Cell. from the KRIBB Research Initiative
cardiomyocytes 35(6): 830-849 Program by the National Research
 Compound 251 inhibited ferroptosis Virpi T. and Heikki R. (2016) Cardiac Foundation of Korea (NRF) funded by the
under cysteine and methionine fibrosis in myocardial infarction – from Korean government (NRF-
deficiency conditions
 Further investigation is required in repair and remodeling to regeneration. 2019R1C1C1002831).
order to elucidate the mechanism for Cell Tissue Res. 365(3):563-581
the inhibition of ferroptosis Wan Seok Yang and Brent R. Stockwell Contact information
 Inhibition of ferroptosis in (2016) Ferroptosis: Death by lipid
cardiomyocytes may provide a novel peroxidation. Trends in cell biology. 26(3): Jeong Eun Lee (jungeun1008@kribb.re.kr)
therapeutic approach for treating 165-176
myocardial infarction Eun-Woo Lee (ewlee@kribb.re.kr)