Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations. Recent studies revealed that abnormal gene expression induced by epigenetic changes including aberrant promoter methylation plays a critical role in human breast carcinogenesis. Cucurbitacin B has antiproliferative activity against various human breast cancer cells, but the molecular mechanism is not completely understood. In this study, we explore the influence of cucurbitacin B from Trichosanthes cucumerina on the methylation status at the promoter of oncogenes c-Myc, cyclin D1, and survivin in breast cancer cell lines. Growth inhibitory effect of cucurbitacin B on breast cancer cells was assessed by MTT assay and colony formation assay. Methylation status of genomic DNA was determined by methylation-specific PCR. Gene and protein expression levels of all genes studied were analyzed by real-time RT-PCR and western blot. The results indicated that cucurbitacin B could inhibit cell growth in breast cancer cells. The oncogene promoters are usually hypomethylated in cancer cells. Upon cucurbitacin B treatment, upregulation of DNMT1 and obvious heavy methylation in the promoters of c-Myc, cyclin D1, and survivin, which consequently downregulated the expression of all these oncogenes, were observed. Hence, cucurbitacin B proved to be a potential cancer therapeutic agent, in part by inducing hypermethylation and silences the oncogenic activation.
Background Dysregulation of immune response is associated with development of endometriosis. The study aim was to evaluate effect of combined oral contraceptive pills (COCs) consisting of ethinyl estradiol (EE) and desogestrel on the expression of macrophage, natural killer cells, and regulatory T cells of ovarian endometriotic cysts. Methods Endometriotic cyst wall tissues were collected from women with endometriosis who were treated (n = 22) with COCs (one table per day of EE 0.03 mg and desogestrel 0.15 mg administered for 28 to 35 days before surgery) or untreated (n = 22). The tissues were collected from endometriotic cyst wall during laparoscopic or laparotomy ovarian cystectomy. Immunohistochemistry for anti-CD68, anti-CD56, and anti-forkhead–winged helix transcription factor (FoxP3), a marker for macrophages, natural killer cells, and regulatory T cells, respectively, were investigated. Results The median (interquartile range [IQR]) number of anti-CD68 positive cells in the COC group was significantly lower than in the untreated group (12.7; 4.9–19.3) versus 45.7 (26.0–70.7), p < 0.001). Tissue infiltration of anti-CD56 positive cells in endometriotic cyst was significantly higher after the treatment when compared with tissue from untreated group (42.9, 27.4–68.9 versus 25.3 (14.1–37.3; p = 0.009). The number of regulatory T cells was also significantly increased in the COC group (6.3, 2.8–15.5) versus 0 (0–1.8; p < 0.001). Conclusions The effects of COC, containing EE 0.30 mg with desogestrel 0.15 mg, on the immune system was demonstrated by a significant decrease in the number of macrophages and an increase in natural killer and regulatory T cells.
Objective: Since endometriosis is an estrogen-dependent disease; therefore, combined oral contraceptives (COCs) may not be the best choice for the treatment of endometriosis. The objective of the present study was to investigate the effects of ethinyl estradiol (EE) and desogestrel (DSG) in COCs on cell proliferation and apoptosis in ectopic endometrial tissue as compared to DSG alone. Materials and methods: Forty-five women of reproductive age with at least one endometriotic cyst were recruited into this single-blind randomized controlled trial study and randomly divided equally into three groups. EE-DSG and DSG groups received EE (0.03 mg) and DSG (0.15 mg) or DSG alone daily for 28-35 days before surgery. The control group was prescribed nothing. Endometriotic cyst tissues were collected during ovarian cystectomy for immunohistochemistry. Results: Levels of Ki-67 positive cells in the ectopic endometrial tissue of the EE-DSG group were significantly higher than the DSG group (median [IQR]; 1.4[1.2] vs 0.6 [0.7], P <0.016). There were significantly more TUNEL-positive cells in the EE-DSG group compared to the DSG group (median [IQR]; 2.8[0.7] vs 1.8[1.4], P < 0.016, respectively). Moreover, the number of TUNEL-positive cells in the EE-DSG and DSG groups were significantly higher than the control (median [IQR]; 2.8[0.7] vs 0.2[0.2] and 1.8[1.4] vs 0.2[0.2], P <0.016). The levels of cells that positively stained for Bcl2 were not different among all groups. Conclusion: Progestin alone increased cell apoptosis in ectopic endometria. However, concurrent EE in COCs enhanced proliferation and promoted a greater apoptotic effect in ectopic endometria compared to progestin alone.
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