As the second most common cancer in men around the world, prostate cancer is increasingly gaining more attention. Dihydroartemisinin (DHA) has been proven to be a promising anticancer agent in vitro as well as in vivo in accumulating data. However, the detailed mechanisms of how DHA action in human prostate cancer PC-3 cells remain elusive. This study aimed to investigate the effects of DHA, a novel anticancer agent, by inhibiting the expression of ubiquitin like containing PHD and ring finger 1 (UHRF1) in PC-3 cells. The apoptosis and cell-cycle distribution were detected by flow cytometry. Quantitative real-time PCR was performed to examine both UHRF1 and DNA methyltransferase 1 (DNMT1) expressions at mRNA levels, whereas the expressions of UHRF1, DNMT1, and p16 proteins at protein levels were detected by Western blotting. Methylation levels of p16 CpG islands were determined by bisulfite genomic sequencing. We showed that DHA induced the downregulation of UHRF1 and DNMT1, accompanied by an upregulation of p16 in PC-3 cells. Decreased p16 promoter methylation levels in DHA-treated groups were also observed in PC-3 cells. Furthermore, DHA significantly induced apoptosis and G1/S cell-cycle arrest in PC-3 cells. Our results suggested that downregulation of UHRF1/DNMT1 is upstream to many cellular events, including G1 cell arrest, demethylation of p16, and apoptosis. Together, our study provides new evidence that DHA may serve as a potential therapeutic agent in the treatment of prostate cancer.
The cognitive dysfunction associated with type 2 diabetes mellitus (T2DM) has been widely studied, and many structures in the hippocampus, such as neurons and synapses, have been shown to play a crucial role in the cognitive decline. However, the mechanism of these changes remains unknown. To further explore this issue, we investigated the changes in the blood supply of the hippocampus in transgenic T2DM mice. In the current study, histochemistry, immunohistochemistry, and unbiased stereological methods were utilized to research the effects of T2DM on hippocampal capillaries of transgenic db/db mice. Twenty (Leprdb) mut/mut mice and twenty (Leprdb) wt/wt mice were used in this study. The learning and memory ability was appraised by Morris water maze test.
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