BackgroundBreast cancer-related mortality increases annually. The efficacy of current breast cancer treatments is limited, and they have numerous side effects and permit high recurrence. Patients with estrogen receptor (ER)-negative or triple-negative breast cancer are particularly difficult to treat. Treatment for this type of cancer is lacking, and its prognosis is poor, necessitating the search for alternative treatments.MethodsThis study screened Chinese herb Hibiscus syriacus extracts and identified a novel anti-cancer drug for patients with ER-negative breast cancer. The inhibitory effects on cell viability and migration were evaluated for each compound, and the molecular regulatory effects were evaluated on both mRNA and protein levels.ResultWe found several triterpenoids including betulin (K02) and its derivatives (K03, K04, and K06) from H. syriacus inhibited human triple-negative breast cancer cell viability and migration but revealed smaller cytotoxic effects on normal mammalian epithelial cells. Betulin and its derivatives induced apoptosis by activating apoptosis-related genes. In addition, they activated p21 expression, which induced cell cycle arrest in breast cancer cells. Betulin (K02) and betulinic acid (K06) had stronger inhibitory effects on cell viability and migration than K03 and K04.ConclusionsH. syriacus extracts might inhibit breast cancer cell viability and induce apoptosis by activating p53 family regulated pathways and inhibiting AKT activation. H. syriacus extracts may provide important insight into the development of novel alternative therapies for breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0592-9) contains supplementary material, which is available to authorized users.
The function of a protein is generally related to its subcellular localization. Therefore, knowing its subcellular localization is helpful in understanding its potential functions and roles in biological processes. This work develops a hybrid method for computationally predicting the subcellular localization of eukaryotic protein. The method is called EuLoc and incorporates the Hidden Markov Model (HMM) method, homology search approach and the support vector machines (SVM) method by fusing several new features into Chou's pseudo-amino acid composition. The proposed SVM module overcomes the shortcoming of the homology search approach in predicting the subcellular localization of a protein which only finds low-homologous or non-homologous sequences in a protein subcellular localization annotated database. The proposed HMM modules overcome the shortcoming of SVM in predicting subcellular localizations using few data on protein sequences. Several features of a protein sequence are considered, including the sequence-based features, the biological features derived from PROSITE, NLSdb and Pfam, the post-transcriptional modification features and others. The overall accuracy and location accuracy of EuLoc are 90.5 and 91.2 %, respectively, revealing a better predictive performance than obtained elsewhere. Although the amounts of data of the various subcellular location groups in benchmark dataset differ markedly, the accuracies of 12 subcellular localizations of EuLoc range from 82.5 to 100 %, indicating that this tool is much more balanced than other tools. EuLoc offers a high, balanced predictive power for each subcellular localization. EuLoc is now available on the web at http://euloc.mbc.nctu.edu.tw/.
Estrogen induces ERα-positive breast cancer aggressiveness via the promotion of cell proliferation and survival, the epithelial-mesenchymal transition, and stem-like properties. Integrin β4 signaling has been implicated in estrogen/ERα-induced tumorigenicity and anti-apoptosis; however, this signaling cascade poorly understood. ΔNp63, an N-terminally truncated isoform of the p63 transcription factor, functions as a transcription factor of integrinβ4 and therefore regulates cellular adhesion and survival. Therefore, the aim of the present study was to investigate the estrogen-induced interaction between ERα, ΔNp63 and integrin β4 in breast cancer cells. In ERα-positive MCF-7 cells, estrogen activated ERα transcription, which induced ΔNp63 expression. And ΔNp63 subsequently induced integrin β4 expression, which resulted in AKT phosphorylation and enhanced cell viability and motility. Conversely, there was no inductive effect of estrogen on ΔNp63-integrinβ4-AKT signaling or on cell viability and motility in ERα-negative MDA-MB-231 cells. ΔNp63 knockdown abolishes these estrogen-induced effects and reduces cell viability and motility in MCF-7 cells. Nevertheless, ΔNp63 knockdown also inhibited cell migration in MDA-MB-231 cells through reducing integrin β4 expression and AKT phosphorylation. In conclusion, estrogen enhances ERα-positive breast cancer cell viability and motility through activating the ERα-ΔNp63-integrin β4 signaling pathway to induce AKT phosphorylated activation. Those findings should be useful to elucidate the crosstalk between estrogen/ER signaling and ΔNp63 signaling and provide novel insights into the effects of estrogen on breast cancer progression.
BackgroundUrinary tract infections (UTIs) are among the most common bacterial infections in pregnant women due to anatomic and physiologic changes in the female urinary tract during pregnancy, and antepartum UTIs can cause adverse pregnancy outcomes that may induce mental stress. There have only been a few studies, however, investigating antepartum UTIs and mental stress. As such, the present study was conducted in order to investigate the association between antepartum UTIs and postpartum depression (PPD).MethodsWe used data from the 2000–2013 National Health Insurance Research Database (NHIRD) of Taiwan. Data regarding a total of 55,087 singleton pregnancies was utilized, including data regarding 406 women who were newly diagnosed with PPD in the first 6 months postpartum. The associations between PPD and antepartum UTIs or other risk factors were examined by multiple logistic regression analysis.ResultsThe logistic regression analysis results indicated that PPD was associated with antepartum UTIs (adjusted odds ratio [aOR] 1.27; 95% confidence interval [CI] (1.07–1.65). Furthermore, the risk of PPD was higher in women with an upper antepartum UTI (aOR 2.97 (1.31, 6.77) than in those with a lower antepartum UTI (aOR 1.21 (1.02, 1.58)).ConclusionsAntepartum UTIs, particularly upper antepartum UTIs, are significantly associated with PPD. This information may encourage physicians to pay greater attention to the mental health of women who have suffered upper UTIs during their pregnancies.
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