Evidences for involvement of estrogen receptor induced ERK1/2 activation in ovarian cancer cell proliferation by Cadmium Chloride.

Cadmium (Cd) as a human carcinogen and one of the most toxic industrial and environmental pollutant mimics the estrogenic effects in cell proliferation. So, it might have a role in the incidence and etiology of hormone-related cancers such as ovarian cancer as the most lethal gynecologic malignancy. This study aimed to evaluate the estrogenic effect and underlying mechanism of Cd in ovarian cancer cell line proliferation. OVCAR3 and SKOV3 cell lines were treated with different concentrations of CdCl2 (0- 50 µM). Cell proliferation was analyzed using MTT and BrdU assay. To evaluate the estrogenic effect of Cd, the cells were pre-incubated with estrogen receptor (ER) antagonist ICI 182,780. The expression of ER was determined using western blotting method. Real-time RT-PCR method was used to assess c-fos, c-jun and FOXO3a mRNA level. The results showed that Cd has an estrogenic proliferative effect at nM concentration range and ICI 182,780 significantly reversed the CdCl2-induced cell proliferation. Cd also increased the expression of ERs. Cd exposure induced activation of p-ERK1/2 in these cells. Cd also intensified c-jun, c-fos, and FOXO3a mRNA expression. Taken together, the current work suggests that Cd induces ovarian cancer cell proliferation in an ER-dependent mechanism induced ERK1/2 activation pathway. Understanding of downstream targets by which Cd deregulates cell proliferation can be noteworthy to define its underlying carcinogenesis mechanism.

The protective role of melatonin in cadmium-induced proliferation of ovarian cancer cells.

Cadmium (Cd), a ubiquitous environmental and occupational pollutant, acts as a metalloestrogen to induce cell proliferation. It is suggested that Cd may also contribute to the development of estrogen-related cancers like ovarian cancer which is the most lethal cancer in women. Furthermore, it was shown that melatonin has antiproliferative effect on estradiol (E2)-induced proliferation. The aim of the present study was to evaluate whether melatonin inhibits Cd-induced proliferation in ovarian cancer cell lines and also whether Cd and melatonin can modulate estrogen receptor α (ERα) expression. OVCAR3 and SKOV3 human ovarian cancer cell lines were treated with CdCl2 (1-100 nM) and melatonin (1 µM) for 48 h. Cell proliferation evaluation was carried out by bromodeoxyuridine (BrdU) incorporation assay. ERα expression was detected by western blotting method 24 h after cell treatment. The results were demonstrated that Cd increased proliferation of ovarian cancer cell lines in a dose dependent manner. Melatonin inhibited Cd-induced proliferation of OVCAR3 and SKOV3 cell lines. Moreover, CdCl2 significantly increased ERα expression in both OVCAR3 and SKOV3 cell lines compared to control. Melatonin significantly inhibited Cd inducing effect on ERα expression of OVCAR3 and SKOV3 cell. In conclusion, due to the proliferative effect on ovarian cancer cell lines, Cd could play an important role in the etiology of ovarian cancer by inducing cells ERα expression. Furthermore, melatonin has the protective role on Cd-induced cell proliferation by inhibition of ERα expression.

Cadmium induces progesterone receptor gene expression via activation of estrogen receptor in human ovarian cancer cells.

Cadmium (Cd) as a metalloesterogen may have a role in development of ovarian cancer. One of the critical target genes of estrogens is progesterone receptors (PRs). There are controversial studies on association between Cd, PRs, and cell proliferation. This study investigates the effect of Cd on proliferation of ovarian cancer cell lines, PRA and PRB expression and their relationship. OVCAR3 and SKOV3 cells were treated with CdCl2 (1-100 nM) and cell proliferation was assayed using bromodeoxyuridine (BrdU) method. The mechanism underlying the proliferative effect of Cd mediated by PRs was examined using cell transfection with PR- small interfering RNA (siRNA) and western blot analysis. Our results showed the involvement of PRs in Cd induced proliferation of ovarian cancer cells. Progesterone receptors are involved in proliferative effect of Cd. Moreover, Cd modified the expression of PRA and PRB and induced ovarian cancer cell proliferation through the change of PRA/PRB ratio. In conclusion, there is a mechanistic association between Cd effects on ovarian cancer cell proliferation, estrogen receptors and PRs expression.

Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review.

BACKGROUND: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. METHODS: All of the observational, case-control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. RESULTS: At the first search, it was fined 1015 articles which included "synaptic plasticity" OR "neuronal plasticity" OR "synaptic density" AND memory AND "molecular mechanism" AND "calcium/calmodulin-dependent protein kinase II" OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. CONCLUSIONS: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory.

Biomarkers for evaluation of prostate cancer prognosis.

Prostate cancer, with a lifetime prevalence of one in six men, is the second cause of malignancy-related death and the most prevalent cancer in men in many countries. Nowadays, prostate cancer diagnosis is often based on the use of biomarkers, especially prostate-specific antigen (PSA) which can result in enhanced detection at earlier stage and decreasing in the number of metastatic patients. However, because of the low specificity of PSA, unnecessary biopsies and mistaken diagnoses frequently occur. Prostate cancer has various features so prognosis following diagnosis is greatly variable. There is a requirement for new prognostic biomarkers, particularly to differentiate between inactive and aggressive forms of disease, to improve clinical management of prostate cancer. Research continues into finding additional markers that may allow this goal to be attained. We here selected a group of candidate biomarkers including PSA, PSA velocity, percentage free PSA, TGFß1, AMACR, chromogranin A, IL-6, IGFBPs, PSCA, biomarkers related to cell cycle regulation, apoptosis, PTEN, androgen receptor, cellular adhesion and angiogenesis, and also prognostic biomarkers with Genomic tests for discussion. This provides an outline of biomarkers that are presently of prognostic interest in prostate cancer investigation.