Aloe-Emodin Induces Mitochondrial Dysfunction and Pyroptosis by Activation of the Caspase-9/3/Gasdermin E Axis in HeLa Cells.

Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), derived from some Chinese edible medicinal herbs, exerts a potential anticancer activity on various cancer cells, making it a drug candidate for cancer therapy. Yet, the role of aloe-emodin in pyroptosis, a new type of cell death, is uncharacterized. In this study, we explored the molecular mechanisms of aloe-emodin-triggered pyroptosis. Aloe-emodin inhibited proliferation and migration and triggered caspase-dependent cell death of HeLa cells in a dose-dependent manner. Aloe-emodin caused mitochondrial dysfunction and induced pyroptosis by activating the caspase-9/3/GSDME axis. Transcriptional analysis showed extensive changes in gene expressions in cellular pathways, including MAPK, p53, and PI3K-Akt pathways when treated with aloe-emodin. This study not only identified a novel role of aloe-emodin in pyroptotic cell death, but also performed a systematical genome-wide analysis of cellular pathways responding to aloe-emodin, providing a theoretical basis for applying anthraquinone derivatives in the treatment of GSDME-expressing cancers.

An investigation of the ability of elemene to pass through the blood-brain barrier and its effect on brain carcinomas.

OBJECTIVES: Elemene is a chemical extracted from plants. It has demonstrated anti-tumour capability. Although widely studied, there has been little reported regarding its tissue distribution. Our aim was to rectify this. METHODS: The tissue distribution of elemene was studied after intragastric or intravenous administration in rats. The effectiveness of elemene in treating brain tumours was studied using the G-422 tumour cell model in mice. KEY FINDINGS: Elemene had a higher concentration in the lungs, spleen and livers than other tissues of normal rats after intragastric and intravenous administration, while the concentration in the gastrointestinal tract was greater after intragastric administration. Elemene molecules were also detected in the rats' brain tissue. Elemene had a therapeutic effect on mice inoculated with G-422 cells both intracranially and subcutaneously. The best life-extending rate and the best tumour-inhibiting rate of elemene were 64.43% and 34.46%, respectively, when 80 mg/kg elemene was used for treatment. CONCLUSIONS: The results from the tissue distribution study showed that elemene can pass through the blood-brain barrier. The therapeutic experiments showed that elemene is effective in treating cerebral malignancy.