Abstract
Objective The aim of the study was to investigate the antiprostate cancer effects and mechanism of ineupatolide (T-21), a natural product isolated from the Compositae plant Carpesium cernuum L., on PC-3 human prostate cancer cells. Methods The effect of T-21 on the proliferation of PC-3 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell migration, and invasion experiments; the morphology of cell apoptosis was observed by Hoechst-propidium iodide staining; the effects of T-21 on PC-3 cell apoptosis and the cell cycle were evaluated by flow cytometry; and the effect of T-21 on the expression levels of phosphorylated protein kinase B (p-AKT), AKT, X-linked inhibitor of apoptosis protein (xlAP), procaspase-3, and poly (ADP-ribose) polymerase (PARP) in PC-3 cells was measured by western blotting. Results T-21 significantly inhibited the proliferation of cells, and its half-maximal inhibitory concentrations at 12, 24, and 48 h were 38.46 ± 1.01, 24.63 ± 0.70, and 7.36 ± 0.58 μM, respectively. T-21 may promote cell apoptosis in a concentration-dependent manner and block the cell cycle in the G2 and S phases. In addition, T-21 significantly reduced the protein expression levels of p-AKT, AKT, xlAP, procaspase-3, and PARP. Conclusion T-21 exhibits antiproliferation effects on PC-3 cells by promoting apoptosis and arresting the cell cycle in the G2 and S phases. The possible mechanism underlying its potential therapeutic effects against prostate cancer is related to the AKT/xlAP pathway.
Highlights
Prostate cancer, which ranks second in the global incidence of male cancers and sixth in mortality, is currently one of the diseases with the highest mortality in middle-aged and elderly men around the world [1]
After treating PC-3 cells with 10, 20, or 40 μM T-21 for 24 h, the expression levels of p-AKT, AKT, X-linked inhibitor of apoptosis protein (xlAP), procaspase-3, and poly (ADPribose) polymerase (PARP) gradually decreased. These results demonstrate a significant effect of promoting PC-3 cell apoptosis, which may be related to the downregulation of the expression levels of AKT/xlAP pathway-related proteins
It has been reported that prostate cancer patients are prone to bone metastasis and severe bone pain in the advanced stage, which seriously affects their quality of life [17]
Summary
Prostate cancer, which ranks second in the global incidence of male cancers and sixth in mortality, is currently one of the diseases with the highest mortality in middle-aged and elderly men around the world [1]. The incidence of prostate cancer gradually increases with age. With the development of the disease, the urethra is gradually compressed by the prostate, which may cause dysuria, sexual dysfunction, and hematuria [4]. In terms of clinical diagnosis, most patients are already at an advanced stage, with local invasion and distant metastasis. In these cases, the effect of surgery is not ideal, or the opportunity for radical surgery has already been lost [6, 7]
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