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. 2022 Jul 14;12(1):11996.
doi: 10.1038/s41598-022-16372-3.

Capsaicin induces ferroptosis of NSCLC by regulating SLC7A11/GPX4 signaling in vitro

Xiao-Yan Liu  1 , Dong-Guang Wei  2 , Rong-Shan Li  3
Affiliations

Capsaicin induces ferroptosis of NSCLC by regulating SLC7A11/GPX4 signaling in vitro

Xiao-Yan Liu et al. Sci Rep. .

Abstract

NSCLC is the first cause of cancer-related deaths in China and threatens life expectancy of the people. Novel drugs and treatment strategies are urgently required. Capsaicin is noticed as a potential new drug for lots of tumors due to its anti-proliferative effect on cancer cells. Our study evaluated the roles of capsaicin in NSCLC cells (A549 and NCI-H23) and further explored its underlying mechanisms. Effect of capsaicin treatment on cell viability was determined by MTT assay and IC50 values for A549 and NCI-H23 cells were ascertained. The iron kit detected the total iron levels and the ferric divalent ions levels in A549 and NCI-H23 cells. GSH kit was used to detect the expression of GSH in A549 and NCI-H23 cells. Additionally, mRNA and protein levels of SLC7A11 and GPX4 were analyzed by real-time PCR and western blot analysis. Through MTT assay, we found that 200 μM capsaicin in cultured A549 cells for 48 h could reach the IC50 value, and the condition was 100 μM and 48 h for NCI-H23 cells. Capsaicin increased total iron levels and ferrous ion levels in A549 and NCI-H23 cells in contrast with the control group, whereas the levels of GSH was reduced in contrast with the control group. Besides, mRNA and protein levels of SLC7A11 and GPX4 were decreased significantly in A549 and NCI-H23 cells treated with capsaicin in contrast with the control group. Our study indicated that capsaicin inhibited the proliferation of A549 and NCI-H23 cells and induced ferroptosis by inactivating SLC7A11/GPX4 signaling. Capsaicin could be used as a potential anticancer agent in the treatment of NSCLC.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Capsaicin induced ferroptosis of A549 and NCI-H23 cells. (A) The chemical formula of capsaicin. (B and C) The cell viabilities of A549 and NCI-H23 cells which were treated by capsaicin (0 μM, 50 μM, 100 μM, 200 μM and 300 μM) were detected by MTT assay. (D and E) The cell viability of A549 and NCI-H23 cells which were treated with capsaicin and ZVF (Z-VAD-FMK, 100 μM)/Fer-1 (Ferrostatin-1, 1 μM) were analyzed by MTT assay. The experiments were repeated thrice. (*P < 0.05, **P < 0.01, ***P < 0.001).
Figure 2
Figure 2
The changes of total iron levels, Fe2+ levels, and GSH levels in A549 and NCI-H23 cells. (A and D) The changes of total iron levels in A549 and NCI-H23 cells. (B and E) The changes of Fe2+ levels in A549 and NCI-H23 cells. (C and F) The changes of GSH levels in A549 and NCI-H23 cells. (**P < 0.01, ***P < 0.001).
Figure 3
Figure 3
The expressions of SLC7A11 and GPX4 were analyzed by real-time PCR. (A) SLC7A11 and GPX4 mRNA expressions in A549 cells. (B) SLC7A11 and GPX4 mRNA expressions in NCI-H23 cells. (**P < 0.001, ***P < 0.0001).
Figure 4
Figure 4
The expressions of SLC7A11 and GPX4 were analyzed by Western blotting analysis. (A) SLC7A11 and GPX4 protein expressions in A549 cells. (B) SLC7A11 and GPX4 protein expressions in NCI-H23 cells. (***P < 0.0001).
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