José D. Solano

Coumarin A/AA Induces Apoptosis-Like Cell Death in HeLa Cells Mediated by the Release of Apoptosis-Inducing Factor

It has been demonstrated that naturally occurring coumarins have strong biological activity against many cancer cell lines. In this study, we assessed the cytotoxicity induced by the naturally isolated coumarin A/AA in different cancer cell lines (HeLa, Calo, SW480, and SW620) and in normal peripheral‐blood mononuclear cells (PBMCs). Cytotoxicity was evaluated using the MTT assay. The results demonstrate that coumarin A/AA was cytotoxic in the four cancer cell lines tested and importantly was significantly less toxic in PBMCs isolated from healthy donors. The most sensitive cancer cell line to coumarin A/AA treatment was Hela. Thus, the programmed cell death (PCD) mechanism induced by this coumarin was further studied in this cell line. DNA fragmentation, histomorphology, cell cycle phases, and subcellular distribution of PCD proteins were assessed. The results demonstrated that DNA fragmentation, but not significant cell cycle disruptions, was part of the PCD activated by coumarin A/AA. Interestingly, it was found that apoptosis‐inducing factor (AIF), a proapoptotic protein of the mitochondrial intermembrane space, was released to the cytoplasm in treated cells as detected by the western blot analysis in subcellular fractions. Nevertheless, the active form of caspase‐3 was not detected. The overall results indicate that coumarin A/AA induces a caspase‐independent apoptotic‐like cell death program in HeLa cells, mediated by the early release of AIF and suggest that this compound may be helpful in clinical oncology.

Differential p53 Protein Expression Level in Human Cancer-Derived Cell Lines After Estradiol Treatment

BACKGROUND p53 has a remarkable number of biological activities, including a central role in cell cycle checkpoints, apoptosis, senescence, and maintenance of genomic integrity. Its expression is modified by estradiol in some epithelial cancer-derived cell lines from the reproductive tract. The aim of this study was to evaluate the effect of low and high doses of estradiol in p53 gene expression in epithelial cancer-derived cell lines from the reproductive tract. METHODS p53 gene expression was assessed by Northern and Western blot methods in three human epithelial cancer-derived cell lines after estradiol treatment. RESULTS These indicated that no changes in p53 mRNA content occurred after estradiol treatment at both low (10 nM) and high (1 micro M) doses of estradiol in HeLa, CaLo, and C-33 cell lines. p53 protein content was nearly constant in HeLa and C-33 cell lines at administration of 10 nM of estradiol. However, when estradiol was administered at a higher dose (1 micro M), an increase in p53 protein was observed over time in HeLa and CaLo cell lines. In contrast, estradiol was without variations in C-33. CONCLUSIONS Overall results indicate that estradiol induces variations of p53 protein levels in epithelial cancer-derived cell lines from the reproductive tract in vitro and that this effect may be related with status p53 and/or presence of E6/E7 from human papillomavirus.

Synthesis, cytotoxic activity, DNA binding and molecular docking studies of novel 9-anilinothiazolo[5,4-b]quinoline derivatives

Novel thiazolo[5,4-b]quinoline derivatives were prepared with or without a (2-(azacycloalkyl)ethyl)amino substituent at the 2-position. The effect of the substituent at 2-position on cytotoxic activity, DNA-intercalation and cytotoxic properties were evaluated. Substituents at 2-position bearing an aliphatic amine favored cytotoxicity, while removal of these substituents resulted in low or negligible cytotoxic properties. Additionally, the in silico predicted binding mode of the novel compounds into DNA correlated with the experimental intercalation data. These results suggest a strong influence of the substituent at 2-position on the DNA intercalation properties.