Effects of nemorosone, isolated from the plant Clusia rosea, on the cell cycle and gene expression in MCF-7 BUS breast cancer cell lines.

BACKGROUND: Breast cancer is the cause of considerable morbidity and mortality in women. While estrogen receptor antagonists have been widely used in breast cancer treatment, patients have increasingly shown resistance to these agents and the identification of novel targeted therapies is therefore required. Nemorosone is the major constituent of the floral resin from Clusia rosea and belongs to the class of polycyclic polyisoprenylated benzophenones of the acylphloroglucinol group. The cytotoxicity of nemorosone in human cancer cell lines has been reported in recent years and has been related to estrogen receptors in breast cancer cells. METHODS: Changes induced by nemorosone in the cell cycle and gene expression of the MCF-7 BUS (estrogen-dependent) breast cancer cell line were analyzed using flow cytometry and the RT(2) Profiler PCR array, respectively. RESULTS: In comparison to breast cancer cells without treatment, nemorosone induced discrete cell cycle arrest in the G1 phase and significant depletion in the G2 phase. Moreover, the compound altered the expression of 19 genes related to different pathways, especially the cell cycle, apoptosis and hormone receptors. CONCLUSION: These promising results justify further studies to clarify mechanisms of action of nemorosone, in view of evaluate the possible use of this benzophenone as adjuvant in the treatment of breast cancer.

Neuroprotective action and free radical scavenging activity of Guttiferone-A, a naturally occurring prenylated benzophenone.

Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases and molecules capable of scavenging ROS may be a feasible strategy for protecting neuronal cells. We previously demonstrated a powerful iron-chelating action of Guttiferone-A (GA), a naturally occurring polyphenol, on oxidative stress injuries initiated by iron overload. Here we addressed the neuroprotective potential of GA in hydrogen peroxide and glutamate-induced injury on rat's primary culture of cortical neurons and PC12 cells, respectively, and antioxidant properties concerning scavenging and anti-lipoperoxidative activities in cell-free models. The decrease in cell viability induced by each of the toxins, assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay, was significantly attenuated by GA. In addition, GA was found to be a potent antioxidant, as shown by (i) inhibition of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reduction (EC50=20.0 µM), (ii) prevention against chemically or electrochemically generated superoxide radicals, (iii) inhibition of spontaneous brain lipid peroxidation and (iv) interference with the Fenton reaction. These results indicate that GA exerts neuroprotective effects against H2O2 or glutamate toxicity and its antioxidant activity, demonstrated in vitro, could be at least partly involved. They also suggest a promising potential for GA as a therapeutic agent against neurodegenerative diseases involving ROS and oxidative damage.

Antimicrobial evaluation of the polyisoprenylated benzophenones nemorosone and guttiferone A.

Polyisoprenylated benzophenones have been isolated from plants, particularly in the Clusiaceae family, and their biological properties recently have received considerable attention from a pharmacological point of view. The aim of the study was to investigate the polyisoprenylated benzophenones, nemorosone and guttiferone A, for their antimicrobial effect against a panel of bacteria, fungi and protozoan parasites. They showed a moderate activity against the Gram-positive bacterium Staphylococcus aureus, while no activity was demonstrated against Escherichia coli and the fungi Trichophyton rubrum and Candida albicans. An interesting activity was found for Plasmodium falciparum with IC50 values lower than 1 µm, while cytotoxicity on MRC-5 cells revealed CC50 values of 15.5 and 12.0 µm, respectively, for nemorosone and guttiferone A.

Aristophenones A and B. A new tautomeric pair of polyisoprenylated benzophenones from Garcinia aristata.

A tautomeric pair of new isoprenylated benzophenones, aristophenone A (1a) and B (1b), have been isolated from Garcinia aristata fruits. Their structures has been determined using high-field 2D NMR techniques.

Nemorosone, the major constituent of floral resins of Clusia rosea.

Nemorosone, the major constituent of the floral resin of Clusia rosea was isolated after exhaustive chromatography. This compound was fully characterized as it is in the nature, without methylation as reported before. A keto-enol equilibrium was observed and both isomers were totally characterized by NMR spectroscopic techniques. The previously announced structure for methylnemorosone was corrected on the basis of application of chemical methylation, high field 2D NMR techniques and NOE difference spectroscopy experiments on the natural product. Our studies concluded that an interchange occurred in the assignment of the benzoyl moiety position with an isoprenyl group in that structure.