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Levistilide a Induces Ferroptosis by Activating the Nrf2/HO-1 Signaling Pathway in Breast Cancer Cells
Shangwen Jing1, Yantong Lu1,2, Jing Zhang1
1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
Introduction:
Breast cancer (BC) is the leading female malignancy, with one million new cases diagnosed worldwide per year. However, the current treatment options for BC patients have difficulty achieving satisfactory efficacy. Ferroptosis is a new mode of regulated cell death that plays a key role in the inhibition of tumorigenesis. Levistilide A (LA), as an active compound extracted from Chuanxiong Rhizoma, might prevent the development of tumors by regulating the critical cellular processes of ferroptosis.
Methods:
In this study, the underlying mechanisms of LA on ferroptosis in BC were explored in vitro. The effect of LA on the viability and mitochondrial function of BC cells was determined. Moreover, the effect of LA on the expression levels of key molecules involved in ferroptosis and the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway was evaluated.
Results:
LA significantly reduced cell viability and damaged the mitochondrial structure and function of BC cells in a dose-dependent manner. Furthermore, LA treatment markedly enhanced reactive oxygen species (ROS)-induced ferroptosis by activating the Nrf2/HO-1 signaling pathway.
Conclusion:
These findings suggest that LA may be a potential lead compound for breast cancer therapy by inducing ferroptosis in tumor cells.
Insights
Levistilide A (LA) induces cancer cell death by promoting ferroptosis, a regulated cell death process. This study shows LA activates the Nrf2/HO-1 pathway, offering potential for new breast cancer treatments.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Breast cancer (BC) is a leading global malignancy with limited treatment efficacy.
- Ferroptosis, a regulated cell death, is crucial in suppressing tumor development.
- Levistilide A (LA), from Chuanxiong Rhizoma, may inhibit tumors by modulating ferroptosis.
Purpose of the Study:
- To investigate the mechanisms by which LA induces ferroptosis in BC cells.
- To evaluate the effects of LA on BC cell viability, mitochondrial function, and ferroptosis-related molecules.
- To assess LA's impact on the Nrf2/HO-1 signaling pathway in BC.
Main Methods:
- In vitro experiments were conducted to explore LA's effects on BC cells.
- Cell viability and mitochondrial function assays were performed.
- Expression levels of ferroptosis markers and the Nrf2/HO-1 pathway were analyzed.
Main Results:
- LA significantly reduced BC cell viability and impaired mitochondrial function in a dose-dependent manner.
- LA treatment enhanced reactive oxygen species (ROS)-induced ferroptosis.
- LA activated the Nrf2/HO-1 signaling pathway.
Conclusions:
- Levistilide A demonstrates potential as a therapeutic agent for breast cancer.
- LA induces tumor cell death through ferroptosis.
- Activation of the Nrf2/HO-1 pathway is a key mechanism in LA-mediated ferroptosis.
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