Reactivity and antiproliferative activity of ferrocenyl-tamoxifen adducts with cyclodextrins against hormone-independent breast-cancer cell lines

Hydroxyferrocifen compounds are a new and promising class of ferrocifen-type breast-cancer drug candidates. They possess both endocrine-modulating properties and cytotoxic activity, which come from the tamoxifen skeleton and the presence of a ferrocene moiety, respectively. However, they suffer from reduced solubility in water, which presents a problem for their eventual therapeutic use. Herein, we examined the interactions of hydroxyferrocifen compounds with cyclodextrins (CDs) to evaluate whether or not their electron-transfer oxidation pathways were affected by their inclusion. It has been demonstrated that these inclusion complexes are soluble in pure water, which shows that CDs can be used to deliver these biologically active molecules. Therefore, a series of these compounds has been investigated by cyclic voltametry in various media in the presence of CDs (beta-CD and Me-beta-CD). In methanol, the hydroxyferrocifen compounds exhibited a weak interaction with the CD cavity. These interactions became stronger as the amount of added water increased. The complexation effect between the hydroxyferrocifen compounds and beta-CD was found to be stronger if the CD was partially methylated, which is probably due to hydrophobic effects between the cyclopentadienyl ring and/or the aromatic rings and the methoxy groups. Moreover, it appears that the structure of the hydroxyferrocifen compounds affects both their solubility and their complexation dynamics. Investigations in the presence of pyridine show that the base kinetically favors the dissociation of the ferrocifen-CD complex during the electron transfer step, but does not affect the follow-up reactivity of the electrogenerated ferrocenium cation, which leads eventually to the corresponding quinone methide, as reported in the absence of CD. Accordingly, the cytotoxicity of these beta-CD-encapsulated organometallic complexes in hormone-independent breast-cancer cells (MDA-MB231) were confirmed to be similar to those obtained in the absence of cyclodextrin.     

A novel CuFe2O4@Ag nanocomposite biosynthesized by Spirulina platensis exhibits an anticancer effect on human gastric adenocarcinoma and Michigan Cancer Foundation-7 breast cancer cell lines

In recent years, the increasing cancer incidence and mortality rate has posed a significant challenge to scientists to develop novel therapeutic drugs against cancerous cells. One of the investigated techniques for cancer therapeutics is the green synthesis of nanoparticles (NPs). In this study, we reported the green synthesis and characterization of the CuFe₂O₄@Ag nanocomposite using Spirulina platensis and its cytotoxic activity on two cancer cell lines: human gastric adenocarcinoma (AGS) and Michigan Cancer Foundation-7 (MCF-7) breast cancer. The physical and chemical properties of the biosynthesized nanocomposite were characterized using Fourier-transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray analysis, dynamic light scattering, ultraviolet–visible spectroscopy, scanning electron microscopy, transmission electron microscopy, and zeta potential analyses. The anticancer properties of the CuFe₂O₄@Ag nanocomposite and imatinib drug on both cancer cell lines were evaluated using 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Also, apoptosis induced by the nanocomposite was assessed using annexin V/propidium iodide staining followed by flow cytometry analysis, Hoechst 33432 staining, and caspase-3 activity assay. Finally, the effect of the CuFe₂O₄@Ag nanocomposite on the expression of BAX and BCL2 genes was assessed by real-time polymerase chain reaction. The result of the MTT test showed an increase in the cellular uptake of CuFe₂O₄@Ag nanocomposite and cell viability loss in a concentration-dependent manner with the 50% minimum inhibitory concentration (IC₅₀) of 180 and 220 μg/ml for MCF-7 and AGS cell lines, respectively. The mean expression of BAX was significantly higher than that of BCL2 in cells treated with the nanocomposite. The results of flow cytometry, Hoechst 33432 staining, and caspase-3 activity assay indicated the stimulation of apoptosis through an increase in caspase-3 and nucleus fragmentation. In general, our results demonstrated the cytotoxic activity of the CuFe₂O₄@Ag nanocomposite. However, further in vivo studies are required to evaluate the accumulation of this nanocomposite in organs such as liver, kidneys, brain, and testes and its potential toxic effects.