Safranal, a Crocus sativus L constituent suppresses the growth of K-562 cells of chronic myelogenous leukemia. In silico and in vitro study.

Crocin, a main constituent of Crocus sativus L (saffron), has been found to inhibit the growth of K-562 human chronic myelogenous leukemia (CML) cells expressing Bcr-Abl protein tyrosine kinase activity. The aim of our study is to investigate the ability of the bioactive saffron's constituents, crocin (CRC) and safranal (SFR), to inhibit the Bcr-Abl protein activity employing an in silico approach, as well as the in vitro effect of these compounds on K-562 growth and gene expression of Bcr-Abl. In silico molecular docking studies revealed that mostly SFR can be attached to Bcr-Abl protein, positioned inside the protein's binding cavity at the same place with the drug used in the treatment of CML, imatinib mesylate (IM). The predicted polar interactions and hydrophobic contacts constructing a hydrophobic cavity inside the active site, explain the observed inhibitory activity. Cytotoxicity experiments showed that SFR and CRC mediate cytotoxic response to K562 cells. In vitro studies on the expression of Bcr-Abl gene revealed that SFR and in a lesser degree IM inhibited the expression of the gene, while in contrast CRC induced an increase. The ultimate goal was to evaluate the existence of a potential antitumor activity of saffron's constituents SFR and CRC.

Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells.

A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC50 values of 121-230 µg/ml (MCF-7), 121-184 µg/ml (MDA-MD-23), 175-309 µg/ml (HT29), 159-314 µg/ml (K1), 180-225 µg/ml (786-0) and 134->400 µg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells.

Effect of cobalt(II) complexes with dipyridylamine and salicylaldehydes on cultured tumor and non-tumor cells: synthesis, crystal structure investigations and biological activity.

The synthesis of eight mixed-ligand cobalt(II) complexes with 2,2'-dipyridylamine (dpamH) and substituted salicylaldehydes (X-saloH) was undertaken in an effort to discover new compounds with anticancer activity. The complexes with the general formula [Co(dpamH)(2)(X-salo)]Y, (Y=Br or Cl) were characterized by elemental analyses, FT-IR and UV-visible spectroscopy, magnetic and conductivity measurements. The structures of two of them [Co(dpamH)(2)(5-CH(3)-salo)]Br and [Co(dpamH)(2)(3-OCH(3)-salo)]Cl, as well as of the precursors [Co(dpamH)(3)]Br(2) and [Co(dpamH)(2)Cl(H(2)O)]Cl, were determined by X-ray crystallography revealing octahedral coordination of cobalt(II) and mononuclear complexes. The complexes were thermally stable up to 200 °C in nitrogen atmosphere, studied by simultaneous TG/DTG-DTA technique. The two precursor Co compounds, as well as four of the title compounds, were evaluated for their efficacy as anticancer agents against different cancer and normal human cell lines. The in vitro chemosensitivity of various human cell lines to these Co complexes was evaluated by measuring cell growth inhibition by employing the SRB colorimetric assay. A series of experiments showed a dose-dependent cytotoxic activity of the complexes against all cell lines used. These findings represent a prompting to search for possible interaction of these complexes with other cellular elements of fundamental importance in cell proliferation.

Significant experimental decrease of the hepatocellular carcinoma incidence in C3H/Sy mice after long-term administration of EB1089, a vitamin D analogue.

EB1089, a vitamin D analogue without the acute side effects of 1alpha,25(OH)2D3, the physiologically active form of vitamin D, exerts strong antiproliferative activities in malignant cells, including hepatoma cells in vitro, and in experimental hepatomas in animals as well. It also induces cell cycle arrest and apoptosis in premalignant conditions, suggesting its application in chemopreventive trials. We examined the possible chemopreventive effect of EB1089 on hepatocellular carcinoma (HCC) incidence in C3H/Sy virgin female mice, a strain developing an incidence of 58% spontaneous HCCs. A total of 95 mice, 16 weeks old, were used. EB1089 injections of 0.5 microg/kg of body weight were given IP every other day for 2, 4, and 6 months to 51 mice (18, 19, and 14 mice, respectively). The remaining 44 mice were divided into three control groups, accordingly, and injected with the vehicle solution only. The mice were sacrificed when they appeared moribund because of their disease. The rest were sacrificed at the age of at least 80 weeks. A full autopsy was performed and liver tissue was processed for histological examination. The results obtained show that 3.9% of treated mice developed HCC, exclusively in the 2-month group, compared with 36.4% of HCCs in the control group. Our results suggest that the chemopreventive administration of EB1089 causes a very statistically significant (P < 0.0001) inhibitory effect on HCC incidence of C3H/Sy mice. This effect could be useful in a potential application on the chemopreventive control of HCCs.