Progesterone has a potential protective effect against ovarian carcinoma induced by estrogen. Progesterone is also known to cause apoptosis while tamoxifen induces growth arrest. Therefore, we attempted to determine whether combined treatment with progesterone and tamoxifen has a synergistic effect on anti-cancer activity. Although progesterone is known to cause apoptosis while tamoxifen induces growth arrest in many cancer cells, the detailed action of progesterone and tamoxifen and the anticancer effect of combined treatment have not been tested in ovarian cancer cells. Therefore, we tested the growth and apoptosis activity of progesterone and tamoxifen and the anticancer effect of combined treatment of progesterone and tamoxifen in ovarian cancer cells. Ovarian cancer cells, PA-1, were treated with progesterone, tamoxifen, or a combination of progesterone and tamoxifen. The anti-cancer effects were investigated by use of flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, DNA fragmentation analysis, and Western blot analysis. We found that 100 µM progesterone induced typical apoptosis in PA-1 cells. Treatment of PA-1 cells with 10 µM tamoxifen resulted in an increase in the levels of p21, p27, p16 and phospho-pRb, indicating typical G1 arrest. Co-treatment of PA-1 cells with 100 µM progesterone and 10 µM tamoxifen resulted in typical apoptosis, similar to that induced by treatment with 100 µM progesterone alone. These results indicate that progesterone caused apoptosis and tamoxifen induced G1 arrest. Combined treatment with tamoxifen and progesterone caused apoptosis similar to that induced by treatment with progesterone alone and had no additional anti-cancer effect in ovarian cancer cells.
"The ovarian neoplasms are characterized by changes in their receptor status. They can either be primarily receptor negative or may lose the receptors with disease progression and expression varies with histological subtypes [22–25]. In this study, ER was expressed in 45% of SOCs without any statistically significant difference across the treatment groups. "
[Show abstract][Hide abstract] ABSTRACT: Serous ovarian cancer (SOC) is a significant cause of morbidity and mortality in females with poor prognosis because of advanced stage at presentation. Recently, neoadjuvant chemotherapy (NACT) is being used for management of advanced SOC, but role of tissue biomarkers in prognostication following NACT is not well established. The study was conducted on advanced stage SOC patients (n = 100) that were treated either conventionally (n = 50) or with NACT (n = 50), followed by surgery. In order to evaluate the expression of tissue biomarkers (p53, MIB1, estrogen and progesterone receptors, Her-2/neu, E-cadherin, and Bcl2), immunohistochemistry and semiquantitative scoring were done following morphological examination. Following NACT, significant differences in tumor histomorphology were observed as compared to the native neoplasms. MIB 1 was significantly lower in cases treated with NACT and survival outcome was significantly better in cases with low MIB 1. ER expression was associated with poor overall survival. No other marker displayed any significant difference in expression or correlation with survival between the two groups. Immunophenotype of SOC does not differ significantly in samples from cases treated with NACT, compared to upfront surgically treated cases. The proliferating capacity of the residual tumor cells is less, depicted by low mean MIB1 LI. MIB 1 and ER inversely correlate with survival.
BioMed Research International 04/2014; 2014:401245. DOI:10.1155/2014/401245 · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Second mitochondria-derived activator of caspases (Smac) is a recently identified protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing the inhibitor of apoptosis proteins (IAPs). Our previous study showed that ectopic overexpression of Smac sensitizes drug-resistant tumor cells to TRAIL- or paclitaxel-induced apoptosis in vitro. The present study was designed to explore the effect of the synthesized Smac N7 peptide in a human ovarian cancer cell line and xenograft model. The results showed that the single-agent Smac N7 had a non-cytotoxic effect, but it effectively enhanced TRAIL- or paclitaxel-induced inhibition of cell proliferation in a dose-dependent manner, even in TRAIL-resistant A2780 cells. When Smac N7 was combined with TRAIL or paclitaxel in treating A2780 cell tumor xenografts, synergistic anticancer effects were achieved. Furthermore, the combination therapy caused less damage in normal tissues and more apoptosis in tumor xenografts compared with TRAIL or paclitaxel alone. Increased apoptosis was associated with the downregulation of XIAP, survivin and the increased activity of caspase-3, along with an increased amount of cleaved PARP. In conclusion, this Smac N7 peptide is a promising candidate for ovarian cancer combination therapy, and Smac may be the target for the development of a novel class of anticancer drugs.
[Show abstract][Hide abstract] ABSTRACT: There have been several epidemiologic studies supporting the protective role of pregnancy, although the mechanism is not clear. High level of progesterone, which is crucial in maintaining pregnancy, has been supposed to be one of the causative factors. Progesterone is produced at the corpus luteum in the early pregnancy and the placenta in the late pregnancy period. In several experimental studies, progesterone was reported to induce apoptosis of ovarian cancer cells through intrinsic and extrinsic pathways. In addition, progesterone has been shown to exert its anticancer effect through genomic and non-genomic action. The objective of this review is to discuss the protective mechanism of pregnancy against ovarian cancer focusing on the steroid hormone, progesterone.
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