Aloe emodin 3-O-glucoside inhibits cell growth and migration and induces apoptosis of non-small-cell lung cancer cells via suppressing MEK/ERK and Akt signalling pathways

Abstract

AimsNon-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer with a high mortality rate. Glycosylation of phenolic compounds may increase water-solubility and pharmacological activities and reduce the toxicity of aglycones. This study aimed to evaluate and compare the anticancer effect of aloe emodin 3-O-glucoside (AE3G) and its aglycone, aloe emodin (AE), against NSCLC. Main methodA human adenocarcinoma cell line (A549) and other human non-small cell lung carcinoma cell lines (NCI-H460 cells and NCI-H1299 cells) and BALB/c nu/nu xenograft mice harbouring A549 cells were used as the NSCLC models. Inhibition of cell migration, disruption of mitochondrial membrane potential (MMP), DNA fragmentation, and expression levels of apoptotic proteins were measured by western blot, wound healing assay, JC-1 staining, or TUNEL staining. Histopathological changes in tumour tissues were observed by H&E and TUNEL staining. ResultsWith no significant cytotoxicity against noncancerous cells (Vero cells), AE3G (5–50 μM) significantly and more effectively inhibited the growth, attachment, migration, Bcl-2 expression, and activation of MEK/ERK and Akt signalling proteins and induced cytochrome c release and Bax expression in A549 cells than AE. AE3G also significantly decreased the growth of other NSCLC cells, NCI-H460 cells and NCI-H1299 cells. AE3G suppressed the mRNA expression of matrix metalloproteinases, MMP2 and MMP9, and augmented the collapse of the mitochondrial MMP, cleavage of caspases (caspase 9, 8, and 3) and PARP, and DNA fragmentation. Intraperitoneal injection of AE3G (13 and 26 mg/kg/day) reduced the tumour volume and weight and induced apoptotic cell death in tumour tissues of xenograft NSCLC mice. SignificanceThe present study demonstrated that AE3G significantly and more effectively diminished human NSCLC cell growth and migration by triggering mitochondria-dependent intrinsic apoptosis than AE, providing AE3G as a new potent candidate to prevent or treat human NSCLC.