Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells.

In this report we determine the ability of ursolic acid (UA) to induce apoptosis and to modulate glucocorticoid receptor (GR) and Activator Protein-1 (AP-1) in MCF-7 cells. The UA-induced apoptosis (53 microM), the PARP cleavage, and the decrease in Bcl-2 protein (53 microM) support the notion that UA induces apoptosis through the intrinsic mitochondrial pathway. UA binds GR (relative binding affinity: 2.57) and translocates GR into nucleus, suggesting its potential as a GR modulator. UA had no effect on GRE- or TRE-driven gene expression. In summary, UA is a GR modulator and may be considered as a potential anticancer agent in breast cancer.

Ursolic acid, a naturally occurring triterpenoid, demonstrates anticancer activity on human prostate cancer cells.

PURPOSE: Glucocorticoids are widely used as adjuvant therapy in hormonal refractory prostate cancer; their therapeutic role, however, remains unclear. Ursolic acid, a natural triterpene, structurally similar to dexamethasone, exhibits antitumor effects in various cell types. Our main objective was to investigate the effects of ursolic acid on cell viability, apoptosis and bcl-2 protein, in human hormone refractory and androgen-sensitive prostate cancer cells. METHODS: The ursolic acid-induced changes in cell viability, apoptosis and bcl-2 protein were examined in human hormone refractory prostate cancer PC-3 cells and androgen-sensitive LNCaP cells, by MTT assay, flow cytometry and western blot analysis, respectively. RESULTS: Ursolic acid inhibited significantly the cell viability and induced apoptosis in PC-3 cells at 55 microM and in LNCaP cells at 45 microM associated with a downregulation of bcl-2 protein. CONCLUSIONS: The antiproliferative and apoptotic effects of ursolic acid in PC-3 and LNCaP cells implicate its potential therapeutic use for the treatment of hormone refractory and androgen-sensitive prostate cancer. The downregulation of bcl-2 may be one of the molecular mechanisms via which it induces apoptosis in PC-3 and LNCaP cells.

Assessment of antioxidant activity of extracts from unique Greek varieties of Leguminosae plants using in vitro assays.

BACKGROUND: It is believed that legumes are a very good source of micronutrients and phytochemicals that present chemopreventive activity against diseases such as diabetes, coronary heart disease and colon cancer. Methanolic and aqueous extracts from 11 unique varieties of Leguminosae family plants cultured in Greece were tested using three different in vitro assays in order to investigate the mechanisms by which phytochemicals present in these legumes exert their chemoprevention. MATERIALS AND METHODS: The extracts were tested by the 1, -diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, the hydroxyl radical- and the peroxyl radical-induced DNA strand scission assays. Hydroxyl (OH*) and peroxyl (ROO*) radicals were generated from ultraviolet (UV) photolysis of hydrogen peroxide (H2O2) and thermal decomposition of 2,2'-azobis-(2-amidinopropane hydrochloride) (AAPH) respectively. RESULTS: In the DPPH assay, all the tested extracts displayed potent radical scavenging efficiency. Furthermore, most of the Leguminosae family plant extracts exerted significant protective activity against DNA damage induced by both reactive oxygen species, although they were more effective in inhibiting ROO*-induced rather than OH*-induced DNA strand scission. CONCLUSION: The results suggest that the free radical scavenging activity of Leguminosae plants may be one of the mechanisms accounting for their chemoprevention.

Furomegistines I and II, two furanopyridine alkaloids from the bark of Sarcomelicope megistophylla.

Two alkaloids, furomegistine I (1) and furomegistine II (2), were isolated from the bark of Sarcomelicope megistophylla. Their structures have been elucidated on the basis of MS and NMR data. Both belong to the category of furanopyridine alkaloids and should be considered as oxidation products of a furo[2,3-b]quinoline precursor. The two alkaloids exhibited moderate cytotoxic activity.

Antileukemic activity of synthetic daunomycinone derivatives bearing modifications in the glycosidic moiety.

The antileukemic activities of the daunomycinone glycosides synthesized in our laboratories (compounds 4 and 7, code names S12 and S13, respectively) were characterized in L1210 cells in vitro. S13 inhibits tumor cell proliferation and viability at day 4 (IC50: 150-200 nM) more effectively than S12 (IC50: 250-450 nM), suggesting that the 4'-trifluoracetamido substitution of the glycosidic moiety of these 3'-halo daunonycinone derivatives has greater antitumor potential than the 4'-azido substitution. Since S12 and S13 do not increase but rather decrease the mitotic index of L1210 cells at 24 hours, they are not antitubulin drugs but might arrest the early stages of cell cycle progression. Pretreatments for 1.5-3 hours with S12 and S13 are sufficient to partially inhibit the rates of DNA and RNA syntheses (IC50: 4-10 microM) determined over 30- to 60-minute periods of pulse-labeling in L 1210 cells in vitro, but these daunomycinone glycosides alter neither the cellular transport of purine and pyrimidine nucleosides nor the rate of protein synthesis. After 24 hours, the concentration-dependent induction of DNA cleavage by S13 reaches a plateau at 10 microM but the weaker S12 requires 48 hours to maximally stimulate DNA cleavage like S13. The mechanism by which S13 induces DNA fragmentation is inhibited by actinomycin D, cycloheximide, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethyl ketone, N-tosyl-L-phenylalanine chloromethyl ketone and ZnSO4, suggesting that S13 triggers apoptosis by caspase and endonuclease activation. Since microM concentrations of S12 and S13 are cytostatic and cytotoxic, but do not sufficiently inhibit RNA and protein syntheses to block their own ability to sustain the active process of apoptosis and DNA fragmentation, such 3'-halo daunomycinone glycosides might be valuable to develop new means of polychemotherapy.

Composition and antimicrobial activity of the essential oils of two Origanum species.

The essential oils obtained from the aerial parts of Origanum scabrum and Origaum microphyllum, both endemic species in Greece, were analyzed by means of GC and GC-MS. Forty-eight constituents were identified, representing 98.59 and 98.66% of the oils, respectively. Carvacrol, terpinen-4-ol, linalool, sabinene, alpha-terpinene, and gamma-terpinene were found as the major components. Furthermore, both samples exhibited a very interesting antimicrobial profile after they were tested against six Gram-negative and -positive bacteria and three pathogenic fungi.

Composition and antimicrobial activity of the essential oils of five taxa of Sideritis from Greece.

The chemical compositions of the essential oils obtained from the aerial parts of five taxa of Sideritis were analyzed using various GC-MS techniques. A total of 99 different compounds was identified, and significant differences (qualitative and quantitative) were observed between the samples. The in vitro antimicrobial activity of the essential oils against six bacteria and three fungi is also reported.

New semisynthetic antimicrobial labdane-type diterpenoids derived from the resin "ladano" of Cistus creticus.

The antimicrobial activity of fifteen semisynthetic labdane-type diterpenes derived from the two major natural compounds 3 and 4 of the resin "ladano" of Cistus creticus is reported. The chloroethyl carbamidic esters 15 and 20 showed the strongest antimicrobial activity against Gram(+), Gram(-) bacteria and pathogenic fungi.

Effects of polyphenolic grape extract on the oxidative status of muscle and endothelial cells.

A grape pomace extract enhanced antioxidant mechanisms in muscle and endothelial cells both in the absence and in the presence of oxidative stress-induced agent tert-butyl hydroperoxide (tBHP). In particular, muscle (C2C12) and endothelial (EA.hy926) cells were treated with the extract at noncytotoxic concentrations for 24 h, and the oxidative stress markers, total reactive oxygen species (ROS), glutathione (GSH), thiobarbituric reactive substances (TBARS), and protein carbonyl levels were assessed. The results showed that the grape extract treatment reduced significantly ROS, TBARS, and protein carbonyl levels and increased GSH in C2C12 cells, while it increased GSH and decreased protein carbonyl levels in EA.hy926 cells. In the presence of tBHP, the grape extract treatment in C2C12 cells reduced significantly ROS, TBARS, and protein carbonyls and increased GSH compared with tBHP alone treatment, while, in EA.hy926 cells, the extract decreased significantly TBARS and protein carbonyls but increased GSH. The antioxidant potency of the extract was different between muscle and endothelial cells suggesting that the antioxidant activity depends on cell type. Moreover, the antioxidant activity of the grape extract, in both cell lines, exerted, at least in part, through increase in GSH levels. The present work is the first to report the effects of grape extract shown for skeletal muscle cells.

Acretoside, a new sucrose ester from Aristolochia cretica.

A new sucrose ester, acretoside, has been isolated from the roots of the Greek endemic species Aristolochia cretica and identified as 6-O-p-coumaroyl-beta-D-fructofuranosyl-(2 --> 1)-alpha-D-glucopyranoside (1). In addition, a known sucrose ester, identified as arillatose B, two phenylpropanoid glucose esters, and five derivatives of aristolochic acids have been isolated. Their structures have been elucidated on the basis of MS and NMR data.