Astragaloside attenuates the progression of prostate cancer cells through endoplasmic reticulum stress pathways

Abstract

Astragaloside (As) has been demonstrated extensively to serve roles in a variety of tumor types, including glioma, lung cancer, colorectal cancer, breast cancer and cervical cancer, and has therefore been widely used in Traditional Chinese Medicine. To the best of our knowledge, the present study was the first to investigate the efficacy of the Traditional Chinese Medicine astragaloside on tumor growth and the apoptosis of prostate cancer cells. In addition, further investigation into the underlying molecular mechanisms via the endoplasmic reticulum (ER) stress pathway was also performed. In the present study, the human prostate cancer DU-145 cell line was employed as an experimental model and cells were divided into five treatment groups: Dimethyl sulfoxide (DMSO) group (control), low-dose astragaloside group (L-As; 20 nmol/l), moderate-dose astragaloside group (M-As; 50 nmol/l), high-dose astragaloside group (H-As, 100 nmol/l) and ER stress suppressor group (tauroursodeoxycholic acid; TUDCA). The proliferative ability and apoptosis rate of the DU-145 cells were detected via Cell Counting kit-8 methods and flow cytometry, respectively. Furthermore, the ER stress factors [binding immunoglobulin protein (BiP), C/EBP homologous protein (CHOP) and caspase-12] were assessed through reverse transcription polymerase chain reaction. Additionally, the protein expression levels of inositol-requiring enzyme 1 (IRE1), phosphorylated protein kinase R-like ER kinase (p-PERK), iron-regulated transcriptional activator Aft (AFT)4 and AFT6 were measured detected by western blot analysis. Administration of As significantly reduced the cell viability and promoted apoptosis (P<0.05) in a dose-dependent manner. Expression of ER-stressed genes BiP, CHOP and caspase-12 mRNA was increased by As administration, while TUDCA treatment led to a lower mRNA expression of these genes, compared with the control group. Results of western blot analysis indicated that the protein expression of IRE1, AFT4 and AFT6 was upregulated in the H-As group, and that the ratio of p-PERK/PERK was also higher than in the other groups. The administration of As demonstrated significant therapeutic effects on the proliferation of prostate cancer cells, as well as the expression of related proteins and genes. The results of the present study suggested future clinical potential of As for the treatment of prostate cancer.

Teglicar Induces Apoptosis in HeLa Cervical Cancer Cells via Endoplasmic Reticulum Stress-Mediated Pathway

“…The inhibition of CPT1A has been proved to cause ER stress (Schlaepfer et al 2014). Many studies also found that ER stress was involved in apoptosis (Gwak et al 2016;Puthalakath et al 2007;Tan et al 2018). To illuminate the effect of teglicar on ER stress in HeLa cells, the ER stressrelated proteins (GRP78, ATF6, IRE1, PERK, and CHOP) were detected by western blot assay.…”

Role of Endoplasmic Reticulum Stress in the Anticancer Activity of Natural Compounds

“…Besides the interplay between ER and mitochondrial intrinsic apoptosis pathway, activation of ER-resident caspase, during ER stress, represents another mechanism to induce apoptosis. Indeed, under ER stress, the active form of rodent caspase-12 and human caspase-4 activates caspase-9, which in turn activates caspase-3, triggering apoptosis [ 41 ].…”

Astragaloside IV inhibits cell invasion and metastasis in vulvar squamous cell carcinoma through the TGF-β1/FAK/AKT signaling pathway

“…Previous studies have confirmed the beneficial effects of AS-IV in the therapy of many diseases, including fibrosis, inflammatory, autoimmune and cardiovascular diseases [5,6]. Previous showed that AS-IV is valuable for cancer treatment due to its inhibitory effects on the proliferation, invasion and metastasis in various tumours, such as prostate cancer [7], breast cancer [8], gastric cancer [9], lung cancer [10] and glioma [11]. However, the effects of AS-IV on the invasion and metastasis in VSCC remain unclear.…”