Antitumoral activity of Ficus carica L. on colorectal cancer cell lines.

In traditional medicine, Ficus carica (also known as fig) latex is recognized as a remedy with various therapeutic effects. In the present study we investigated the antitumor activity of Ficus carica extracts and latex. We evaluated the effects of increasing concentrations of Ficus carica extracts and latex on HCT-116 and HT-29 human colorectal cell proliferation using MTT assay and apoptosis induction by evaluating PARP cleavage by Western blot analysis. Peel, pulp, leaves, whole fruit and latex extracts of Ficus carica exerted significant antiproliferative effects on HCT-116 (IC50 values 239, 343, 177, 299, 206 µg/ml) and HT-29 cells (IC50 values 207, 249, 230, 261, 182 µg/ml) after 48h of treatment. Furthermore, treatment with different extracts of Ficus carica induced apoptosis in both HT-29 and HCT-116 cancer cells. Leaves and latex extracts of Ficus carica showed the strongest antiproliferative activities. Overall, our results showed that these natural products are strong apoptosis inducers which suggest their use of for therapeutic purposes.

Association of thoracic aorta calcium and non cardiac vascular events in cardiac disease-free individuals.

OBJECTIVE: Thoracic aorta calcium (TAC) is measurable on the same computed tomography (CT) scan as coronary artery calcium (CAC) but has still unclear clinical value. We assessed TAC and CAC relations with non-cardiac vascular events history in a cohort of subjects at risk for cardiovascular disease. METHODS: We analyzed retrospectively 1000 consecutive subjects having undergone CAC detection by non-contrast multi-slice CT with measurement field longer than usual in order to measure total TAC including aortic arch calcium. We also determined partial TAC restricted to ascending and descending thoracic aorta sites by removing arch calcium from total TAC. Calcium deposits were measured with a custom made software using Agatston score. RESULTS: Compared with the rest of the cohort, the 30 subjects with non-cardiac vascular event history had higher median values [95% CI] of total TAC (282 [28-1809] vs 39 [0-333], p < 0.01) and partial TAC (4 [0-284] vs 0 [0-5], p < 0.01) but no different value of CAC (73 [0-284] vs 16 [0-148]). Odds ratio [95% CI] of having non-cardiac vascular event per 1-SD increase in log-transformed calcium value was significant for total TAC but not for CAC, if total TAC and CAC were entered separately (1.56 [1.12-2.24], p < 0.01 and 1.13 [0.86-1.50], respectively) or together (1.57 [1.10-2.32], p < 0.01 and 0.98 [0.73-1.32], respectively) in the logistic adjusted model. CONCLUSION: TAC assessment simultaneous with CAC detection provides complementary information on the extra coronary component of cardiovascular risk beyond CAC's coronary risk prediction. Further studies are required to prospectively confirm this result.

Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells.

Limited success has been achieved in extending the survival of patients with metastatic colorectal cancer (CRC). There is a strong need for novel agents in the treatment and prevention of CRC. Therefore, in the present study we evaluated the antiproliferative and pro-apoptotic potential of Crataegus azarolus ethyl acetate extract in HCT-116 and HT-29 human colorectal cancer cell lines. Moreover, we attempted to investigate the signaling pathways that should be involved in its cytotoxic effect. The Crataegus azarolus ethyl acetate extract-induced growth inhibitory effect was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential, and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, ethyl acetate extract of Crataegus azarolus induced the cleavage of caspase-8. It has no effect on steady-state levels of total Bcl-2 protein. Whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines. Taken together, these findings confirm the involvement of the extrinsic pathway of apoptosis. The apoptotic cell death induced by ethyl acetate extract of Crataegus azarolus was accompanied by an enhancement of the p21 expression but not through p53 activation in human colorectal cancer cells. The above-mentioned data provide insight into the molecular mechanisms of Crataegus azarolus ethyl acetate extract-induced apoptosis in CRC. Therefore, this compound should be a potential anticancer agent for the treatment of CRC.

Identifying the principal modes of variation in human thoracic aorta morphology.

PURPOSE: Diagnosis and management of thoracic aorta (TA) disease demand the assessment of accurate quantitative information of the aortic anatomy. We investigated the principal modes of variation in aortic 3-dimensional geometry paying particular attention to the curvilinear portion. MATERIALS AND METHODS: Images were obtained from extended noncontrast multislice computed tomography scans, originally intended for coronary calcium assessment. The ascending, arch, and descending aortas of 500 asymptomatic patients (57 ± 9 y, 81% male) were segmented using a semiautomated algorithm that sequentially inscribed circles inside the vessel cross-section. Axial planes were used for the descending aorta, whereas oblique reconstructions through a toroid path were required for the arch. Vessel centerline coordinates and the corresponding diameter values were obtained. Twelve size and shape geometric parameters were calculated to perform a principal component analysis. RESULTS: Statistics revealed that the geometric variability of the TA was successfully explained using 3 factors that account for ∼80% of total variability. Averaged aortas were reconstructed varying each factor in 5 intervals. Analyzing the parameter loadings for each principal component, the dominant contributors were interpreted as vessel size (46%), arch unfolding (22%), and arch symmetry (12%). Variables such as age, body size, and risk factors did not substantially modify the correlation coefficients, although some particular differences were observed with sex. CONCLUSIONS: We conclude that vessel size, arch unfolding, and symmetry form the basis for characterizing the variability of TA morphology. The numerical data provided in this study as supplementary material can be exploited to accurately reconstruct the curvilinear shape of normal TAs.

Triterpene saponins of Genista ulicina Spach.

From the n-BuOH extract of the aerial parts of Genista ulicina, six triterpene saponins, 3-O-ß-D-glucopyranosyl-olean-12-ene-3ß,27,28,30-tetraol, 3-O-ß-D-glucopyranosyl-olean-12-ene-3ß,27,28,29-tetraol, 3,29-di-O-ß-D-glucopyranosyl-olean-12-ene-3ß,27,28,29-tetraol, 3-O-ß-D-glucopyranosyl-olean-12-ene-3ß,28,29-triol-27-oic acid, 3-O-ß-D-glucopyranosyl-olean-12-ene-3ß,27,28-triol-29-oic acid, and 3-O-ß-D-glucopyranosyl-14-H-27-nor-olean-12-ene-3ß,28,29-triol, were isolated together with eight known triterpene saponins and six flavonoids. Their structures were established mainly by means of spectroscopic methods (1D and 2D-NMR as well as HR-ESI-MS). The n-BuOH extract, investigated for its antitumor growth inhibition of human colon cancer HT-29 cells, presented no significant activity (IC50>100 µg).

Phytochemical potential of Daphne gnidium in inhibiting growth of melanoma cells and enhancing melanogenesis of B16-F0 melanoma.

In this study, we have investigated inhibitory capacity of ethyl acetate, total oligomer flavonoid (TOF), aqueous extracts and beta amyrin acetate, a triterpene isolated from ethyl acetate extract obtained from leaves of Daphne gnidium, on mouse melanoma (B16-F0 and B16-F10 cells) proliferation. Influence of these products on percentage cell distribution in cycle phases and melanogenesis was also studied. Cell viability was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and flow cytometry was used to analyse effects of tested compounds on progression through the cell cycle. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm. Ethyl acetate, TOF and aqueous extracts exhibited significant anti-proliferative activity after incubation with the two types of tumour skin cells B16-F0 and B16-F10. Furthermore, cell cycle analysis revealed that cells treated with ethyl acetate and TOF extracts were arrested predominantly in G2-M phase. Ethyl acetate extract has also the ability to enhance melanogenesis and tyrosinase activity of B16-F0 melanoma cells.

Large artery wall thickening and its determinants under antihypertensive treatment: the IMT-INSIGHT study.

BACKGROUND: Calcium antagonists retard progression of intima-media thickness (IMT), but whether this retardation covers heterogeneous individual patient responses of IMT change is unknown. METHODS: Hypertensive patients treated for 4 years with nifedipine (n = 115) or coamilozide (n = 127) underwent ultrasound measurements of carotid IMT at baseline, 4 months later, and then every year. RESULTS: A histogram of individual slopes of IMT change (least square regression of IMT to time) during treatment identified three categories of slopes according to the 20th and 80th percentiles of distribution: lower, intermediate and higher percentiles of IMT slope; the proportion of categories of IMT slope differed between treatments (P < 0.05), due to a more frequent lower slope percentile under nifedipine (27%) than under coamilozide (14%); within-group differences between IMT slope categories were: (i) increased baseline IMT associated with lower IMT slope percentile in nifedipine group (P < 0.001) and (ii) more frequent carotid plaque associated with higher IMT slope percentile in both treatment groups (P < 0.05). Analysis of overall patients showed that IMT slope was associated negatively with nifedipine treatment (P < 0.01) and baseline IMT (P < 0.001) and positively with carotid plaque (P < 0.01); the relationship between IMT slope and baseline IMT was negative under nifedipine and flat under coamilozide, and the presence of plaque reset both relationships towards a higher IMT slope; the between-treatment difference in IMT slope was different between tertiles of baseline IMT (P = 0.016). CONCLUSIONS: The differences in IMT slope between nifedipine and coamilozide increase with increasing baseline IMT.

Ursolic acid induces apoptosis through caspase-3 activation and cell cycle arrest in HaCat cells.

Ursolic acid (UA) is a pentacyclic triterpene compound isolated from many kinds of medicinal plants and present in human diet. In this study, we investigated the pro-apoptotic effect of UA on HaCat derived keratinocyte cell line. Treatment with UA decreased the viability of HaCat cells in a concentration- and time-dependent manner. In addition, cell cycle analysis revealed that UA treated HaCat cells were blocked predominantly in G1 phase. Moreover, expression of p21WAF1, a cell cycle regulator, was increased by UA, indicating that UA-induced cell cycle arrest could be mediated through p21WAF1. During UA treatment, we also demonstrated that p53 was phosphorylated at serine 392 and translocated to the nucleus. It is well established that p53 achieves its tumor suppressor activity by inducing apoptosis on cells. To define the apoptotic process in our system, we examined effect of UA on caspase activities, and demonstrated caspase-3 activation. In conclusion, our results suggest that UA induces: i) cell cycle arrest concomitantly with the apparition of the apoptotic sub group G1 peak, and ii) cell death through apoptosis, which is mediated by caspase-3.

Clinical use of nifedipine GITS in the treatment of hypertension: an overview.

Given the major role of elevated blood pressure in the pathogenesis of both stroke and coronary heart disease, one of the biggest challenges facing public health authorities and medical practitioners is the control of hypertension worldwide, both in individual patients and at the population level. The prevalence of hypertension increases with age and is nearly 60% in people aged 65 - 74 years. With increasing age, polymorbidity and polypharmacy usually contribute to an increasingly complex approach to manage the respective clinical conditions, including the treatment of hypertension. All subgroups of calcium channel blockers are effective and well-tolerated in lowering blood pressure. They are of demonstrated benefit for the prevention of stroke in elderly patients with systolic hypertension. Calcium channel blockers are particularly recommended for elderly patients with systolic hypertension and for black patients. The nifedipine gastrointestinal therapeutic system (GITS) formulation provides a once-daily dosing regimen with a continuous and slow release of the drug, resulting in a smooth plasma concentration/time profile. The INSIGHT study established that nifedipine GITS decreased mortality and morbidity at the same level as standard diuretic treatment in hypertensive patients with additional risk factors. A subgroup analysis showed that the long-term protective effects of nifedipine GITS extended to hypertensive patients with diabetes mellitus and with previous myocardial infarction. Two substudies of INSIGHT showed that nifedipine slowed the progression of atherosclerosis in carotid arteries (intima-media thickness) and coronary arteries (coronary calcium) as compared to diuretic.

Effects of calcium channel blockers on atherosclerosis: new insights.

Atherosclerotic disease is the most frequent cause of death in the western world. The key role of calcium ions in atherogenesis has created interest in the antiatherogenic potential of calcium channel blockers. Nifedipine, administered in a long-acting gastrointestinal transport system (GITS) formulation, was shown to have similar efficacy to the diuretic co-amilozide in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Two side-arm studies of INSIGHT suggest that nifedipine GITS has a greater antiatherosclerotic effect than diuretic therapy, which may signal additional cardiovascular protection in the long term. This paper reviews the evidence for the antiatherogenic properties of calcium channel blockers and discusses their clinical implication.