Dioscin facilitates ROS-induced apoptosis via the p38-MAPK/HSP27-mediated pathways in lung squamous cell carcinoma

Abstract

Lung squamous cell carcinoma (SCC) is one of the deadliest cancers both in China and worldwide. To date, the efficacy of lung SCC treatments is limited. Recent studies have elucidated the powerful anti-tumour role of dioscin in different human cancers. Here, our study aims to investigate the effect of dioscin on lung SCC and its underlying mechanism. First, we found that dioscin not only inhibited cell proliferation and cell migration and induced cell apoptosis in lung SCC cells but also suppressed tumour growth in tumour-bearing mice. Furthermore, we noted that the accumulation of intracellular reactive oxygen species (ROS) was triggered by dioscin in lung SCC cells, leading to the phosphorylation of HSP27 through p38-MAPK and consequent cell apoptosis. The activation of p38-MAPK/HSP27 induced by the p38-MAPK activator Anisomycin enhanced the apoptosis of lung SCC cells, while the ROS inhibitor N-acetyl-L-cysteine (NAC) and the p38-MAPK inhibitor SB203580 both attenuated dioscin-mediated cell apoptosis. Moreover, NAC suppressed the activation of p38-MAPK/HSP27 that induced by dioscin. In conclusion, these results confirm that dioscin facilitates ROS-induced apoptosis via the p38-MAPK/HSP27-mediated pathway in lung SCC.

Human Blood Serum Induces p38-MAPK- and Hsp27-Dependent Migration Dynamics of Adult Human Cardiac Stem Cells: Single-Cell Analysis via a Microfluidic-Based Cultivation Platform

“…Further, the GO-terms ‘p38 MAPK-pathway’ and ‘Integrin signaling pathway’ were found to be enriched in serum treated hCSCs compared to untreated hCSCs [ 17 ]. In contrast, a recent study showed p38-MAPK and phosphorylated Hsp27 to mediate apoptosis of lung squamous cell carcinoma cells [ 32 ], suggesting a potential cell type-specific function of p38-MAPK and Hsp27. These findings also underline the necessity to investigate the molecular dynamics of migration in a cell type-specific manner.…”

“…Hsp27 has been shown to be involved in F-actin assembly and migrative processes of vascular smooth muscle cells [ 30 , 31 ]. However, other studies demonstrated apoptosis of lung squamous cell carcinoma cells upon phosphorylation of Hsp27 [ 32 ], which indicates a potential cell type-specific function of Hsp27.…”

Dioscin: A review on pharmacological properties and therapeutic values

“…Yao et al observed that dioscin exerts its antitumor functions on SCC by studying tumor‐bearing mice treated with dioscin. Dioscin‐inhibited cell proliferation and migration, induced apoptosis and curtailed tumor growth in the mice by triggering the accumulation of intracellular ROS by activating the p38‐MAPK/HSP27‐mediated pathway 62 …”

“…ROS is a subproduct of oxidative energy metabolism and normally controls cell proliferation, differentiation, migration, and death. 62 This dioscin-induced ROS accumulation results in unfavorable changes in cancerous tissue such as DNA damage, structural changes and mitochondrial dysfunction. ROS is responsible for activating different apoptotic pathways to ensure the termination of tumor growth.…”

“…It can be observed that in most dioscin‐treated tumor cells, there is an increase in the generation of intracellular ROS levels. ROS is a subproduct of oxidative energy metabolism and normally controls cell proliferation, differentiation, migration, and death 62 . This dioscin‐induced ROS accumulation results in unfavorable changes in cancerous tissue such as DNA damage, structural changes and mitochondrial dysfunction.…”