Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

<p>Abstract</p> <p>Background</p> <p>Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells.</p> <p>Methods</p> <p>The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth <it>in vivo </it>were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression.</p> <p>Results</p> <p>BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10.</p> <p>Conclusions</p> <p>These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.</p

Validity of 2D lateral cephalometry in orthodontics: a systematic review

Lateral cephalometric radiography is commonly used as a standard tool in orthodontic assessment and treatment planning. The aim of this study was to evaluate the available scientific literature and existing evidence for the validation of using lateral cephalometric imaging for orthodontic treatment planning. The secondary objective was to determine the accuracy and reliability of this technique. We did not attempt to evaluate the value of this radiographic technique for other purposes. A literature search was performed using specific keywords on electronic databases: Ovid MEDLINE, Scopus and Web of Science. Two reviewers selected relevant articles, corresponding to predetermined inclusion criteria. The electronic search was followed by a hand search of the reference lists of relevant papers. Two reviewers assessed the level of evidence of relevant publications as high, moderate or low. Based on this, the evidence grade for diagnostic efficacy was rated as strong, moderately strong, limited or insufficient. The initial search revealed 784 articles listed in MEDLINE (Ovid), 1,034 in Scopus and 264 articles in the Web of Science. Only 17 articles met the inclusion criteria and were selected for qualitative synthesis. Results showed seven studies on the role of cephalometry in orthodontic treatment planning, eight concerning cephalometric measurements and landmark identification and two on cephalometric analysis. It is surprising that, notwithstanding the 968 articles published in peer-reviewed journals, scientific evidence on the usefulness of this radiographic technique in orthodontics is still lacking, with contradictory results. More rigorous research on a larger study population should be performed to achieve full evidence on this topic