Psoralidin induces autophagy through ROS generation which inhibits the proliferation of human lung cancer A549 cells

Abstract

Psoralidin (PSO), a natural furanocoumarin, is isolated from Psoralea corylifolia L. possessing anti-cancer properties. However, the mechanisms of its effects remain unclear. Herein, we investigated its anti-proliferative effect and potential approaches of action on human lung cancer A549 cells. Cell proliferation and death were measured by MTT and LDH assay respectively. Apoptosis was detected with Hoechst 33342 staining by fluorescence microscopy, Annexin V-FITC by flow cytometry and Western blot analysis for apoptosis-related proteins. The autophagy was evaluated using MDC staining, immunofluorescence assay and Western blot analyses for LC3-I and LC3-II. In addition, the reactive oxygen species (ROS) generation was measured by DCFH2-DA with flow cytometry. PSO dramatically decreased the cell viabilities in dose- and time-dependent manner. However, no significant change was observed between the control group and the PSO-treated groups in Hoechst 33342 and Annexin V-FITC staining. The expression of apoptosis-related proteins was not altered significantly either. While the MDC-fluorescence intensity and the expression ratio of LC3-II/LC3-I was remarkably increased after PSO treatment. Autophagy inhibitor 3-MA blocked the production of LC3-II and reduced the cytotoxicity in response to PSO. Furthermore, PSO increased intracellular ROS level which was correlated to the elevation of LC3-II. ROS scavenger N-acetyl cysteine pretreatment not only decreased the ROS level, reduced the expression of LC3-II but also reversed PSO induced cytotoxicity. PSO inhibited the proliferation of A549 cells through autophagy but not apoptosis, which was mediated by inducing ROS production.

Raw and thermally treated cement asbestos exerts different cytotoxicity effects on A549 cells in vitro

“…The complex function of the p53 family members is tightly regulated at different levels including the interactions with a number of other proteins that often results in modifications of their stability, localization and transcriptional activities (Leãoa et al, 2014). Many factors can influence these variations, and in particular, regarding p53, several findings have reported the molecular links between apoptosis and ROS-mediated autophagy in A549 cells (Hao et al, 2014). p53 modulates autophagy through several routes: autophagy is repressed by the cytoplasmic localization of p53 in a non-transcriptional manner, whereas autophagy is enhanced by nuclear localization through transactivation of target genes including DRAM (Damage-Regulated Autophagy Modulator), a pro-autophagic and proapoptotic protein (Lorin et al, 2010).…”

Differential effect of psoralidin in enhancing apoptosis of colon cancer cells via nuclear factor-κB and B-cell lymphoma-2/B-cell lymphoma-2-associated X protein signaling pathways

“…In the present study, psoralidin treatment reduced the viability and promoted the apoptosis of SW480 cells in a dose-dependent manner. Furthermore, Hao et al (18) reported that psoralidin inhibited the proliferation of A549 cells by inducing ROS production. Szliszka et al (25) identified that psoralidin inhibited cell proliferation of prostate cancer cells by enhancement of tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis.…”

“…Current research has revealed that psoralidin contains a number of compounds, including coumarin, flavonoids and monoterpene phenols, which possess immunomodulatory, anti-inflammatory, antioxidant and anti-tumor effects (17). Furthermore, Hao et al (18) reported that psoralidin inhibited the proliferation of A549 human lung cancer cells through the generation of reactive oxygen species (ROS). Additionally, psoralidin has been observed to inhibit cell proliferation and induce apoptosis of androgen-independent prostate cancer cells through phosphatidylinositol 3-kinase-mediated Akt signaling (17).…”

Psoralidin inhibits proliferation and enhances apoptosis of human esophageal carcinoma cells via NF-κB and PI3K/Akt signaling pathways

“…Furthermore, psoralidin was additionally able to decrease the caspase-3 activity of Eca9706 cells in a dose-dependent manner. Hao et al (20) reported that psoralidin was able to inhibit the proliferation of A549 human lung cancer cells via generation of reactive oxygen species. Yang et al (17) reported that psoralidin was able to inhibit cell viability and induce apoptosis in human prostate cancer PC-3 and DU-145 cells.…”

“…Furthermore, Hao et al (20) reported that psoralidin was able to inhibit the proliferation of human lung cancer A549 cells. The present study aimed to provide the first evidence of the anticancer effect of psoralidin on esophageal cancer, and render mechanistic insights into the antitumor action of this compound against human esophageal carcinoma Eca9706 cells.…”