Fascaplysin Induces Apoptosis and Ferroptosis, and Enhances Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer (NSCLC) by Promoting PD-L1 Expression
Fascaplysin is a natural product isolated from sponges with a wide range of anticancer activities. However, the mechanism of fascaplysin against NSCLC has not been clearly studied. In this study, fascaplysin was found to inhibit migration by regulating the wnt/β-catenin signaling pathway and reversi...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/22/13774 |
| Summary: | Fascaplysin is a natural product isolated from sponges with a wide range of anticancer activities. However, the mechanism of fascaplysin against NSCLC has not been clearly studied. In this study, fascaplysin was found to inhibit migration by regulating the wnt/β-catenin signaling pathway and reversing the epithelial–mesenchymal transition phenotype. Further research showed that the anti-NSCLC effect of fascaplysin was mainly through the induction of ferroptosis and apoptosis. Fascaplysin-induced ferroptosis in lung cancer cells, evidenced by increased levels of ROS and Fe<sup>2+</sup> and downregulation of ferroptosis-associated protein and endoplasmic reticulum stress, was involved in fascaplysin-induced ferroptosis. In addition, ROS was found to mediate fascaplysin-induced apoptosis. Fascaplysin significantly upregulated the expression of PD-L1 in lung cancer cells, and enhanced anti-PD-1 antitumor efficacy in a syngeneic mouse model. Therefore, these results suggest that fascaplysin exerts anticancer effects by inducing apoptosis and ferroptosis in vitro, and improving the sensitivity of anti-PD-1 immunotherapy in vivo. Fascaplysin is a promising compound for the treatment of NSCLC. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |