Silene Carneiro do Nascimento

Effects of low-level laser therapy on malignant cells: in vitro study.

The aim of this study was to assess the effect of 635- and 670-nm laser irradiation on H.Ep.2 cells in vitro using MTT. In addition to our previous report on the effects of LLLT on the proliferation of laryngeal carcinoma cells in which it was found that irradiaton H.Ep.2 cells with 670-nm laser results in increased cell proliferation, it was decided to evaluate the effect of increased doses of laser light on these cells. The cells, obtained from SCC of the larynx, were routinely processed from defrost to the experimental condition. The cultures were kept either at 5% or 10% of FBS. Twenty-four hours after transplantation, the cells were irradiated with laser light (5-mW diode lasers; 635 and 670-nm; beam cross section approximately 1 mm) at local light doses between 0.04 and 4.8.10(4) Jm(-2). For 670 nm, significant differences in the proliferation were observed between the two concentrations of FBS (p = 0.002) and between irradiated cultures and controls (p = 0.000). Although the results were not significant, 635-nm irradiated cells also proliferated more than nonirradiated ones. This occurred under both conditions of nutrition. It is concluded, that irradiation with 670-nm laser light applied at doses between 0.04 and 4.810(4) Jm(-2) could significantly increase proliferation of laryngeal cancer cells.

Antiproliferative Activity, Antioxidant Capacity and Tannin Content in Plants of Semi-Arid Northeastern Brazil

The objective of this study was to evaluate antiproliferative activity, antioxidant capacity and tannin content in plants from semi-arid northeastern Brazil (Caatinga). For this study, we selected 14 species and we assayed the methanol extracts for antiproliferative activity against the HEp-2 (laryngeal cancer) and NCI-H292 (lung cancer) cell lines using the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazole) (MTT) method. In addition, the antioxidant activity was evaluated with the DPPH (2,2-diphenyl-2-picrylhydrazyl) assay, and the tannin content was determined by the radial diffusion method. Plants with better antioxidant activity (expressed in a dose able to decrease the initial DPPH concentration by 50%, or IC50) and with higher levels of tannins were: Poincianella pyramidalis (42.95 ± 1.77 µg/mL IC50 and 8.17 ± 0.64 tannin content), Jatropha mollissima (54.09 ± 4.36µg/mL IC50 and 2.35 ± 0.08 tannin content) and Anadenanthera colubrina (73.24 ± 1.47 µg/mL IC50 and 4.41 ± 0.47 tannin content). Plants with enhanced antiproliferative activity (% living cells) were Annona muricata (24.94 ± 0.74 in NCI-H292), Lantana camara (25.8 ± 0.19 in NCI-H292), Handroanthus impetiginosus (41.8 ± 0.47 in NCI-H292) and Mentzelia aspera (45.61 ± 1.94 in HEp-2). For species with better antioxidant and antiproliferative activities, we suggest future in vitro and in vivo comparative studies with other pharmacological models, and to start a process of purification and identification of the possible molecule(s) responsible for the observed pharmacological activity. We believe that the flora of Brazilian semi-arid areas can be a valuable source of plants rich in tannins, cytotoxic compounds and antioxidant agents.

In vitro and in vivo properties of usnic acid encapsulated into PLGA-microspheres.

Microparticles will probably play a promising role in the future of chemotherapy. These polymeric delivery systems are capable of maximizing the therapeutic activity while reducing side effects of anti-cancer agents. Usnic acid (UA) is a secondary metabolite produced by lichens, which exhibits an anti-tumour activity. In this study, PLGA-microspheres containing usnic acid from Cladonia substellata were prepared by the double emulsion method, with or without PEG as stabilizer. The morphology of the microspheres was examined by optical and scanning electron microscopy. The in vitro kinetic profile of usnic acid loaded-microspheres was carried out by dissolution testing. The usnic acid content was analysed by HPLC. The cytotoxicity of free and encapsulated usnic acid was evaluated against HEp-2 cells using the MTT method. The anti-tumour assay was performed in mice against Sarcoma-180 tumour (UA 15 mg kg−1 weight body/day) during 7 days. Animals were then sacrificed and tumour and organs were excised for histopathological analysis. Microspheres presented a smooth spherical surface with a mean diameter of 7.02 ± 2.72 µm. The usnic acid encapsulation efficiency was ∼100% (UA 10 mg 460 mg−1 microspheres). A maximum release of 92% was achieved at the fifth day. The IC50 values for free and encapsulated usnic acid were 12 and 14 µg ml−1, respectively. The encapsulation of usnic acid into microspheres promoted an increase of 21% in the tumour inhibition as compared with the free usnic acid treatment. In summary, usnic acid was efficiently encapsulated into PLGA-microspheres and the microencapsulation improved its anti-tumour activity.

Medicinal plants used as antitumor agents in Brazil: an ethnobotanical approach.

We describe the medicinal plants that have been reported to be antitumor agents and that have been used in ethnobotanic research in Brazil to answer the following questions: what is the abundance of plants reported to be antitumor in Brazil? Have the plant species used for tumor treatment in traditional Brazilian medicine been sufficiently examined scientifically? Our analysis included papers published between 1980 and 2008. A total of 84 medicinal plant species were reported to be used for cancer and tumor prevention or treatment; 69.05% of these were cited as being used for the treatment of tumors and cancer in general and 30.95% for specific tumors or cancers. The plants that were cited at a higher frequency were Aloe vera, Euphorbia tirucalli, and Tabebuia impetiginosa. At least, one pharmacological study was found for 35.71% of the species. Majority of the studies selected were conducted in rural communities and urban areas and in areas with traditional healers in Brazil. We found the following molecules to be the most studied in vitro and in vivo: silibinin, β-lapachone, plumbagin and capsaicin. The species addressed here constitute interesting objects for future studies to various professionals in the field of natural products.

Synthesis, antimicrobial and cytotoxic activities of some 5-arylidene-4-thioxo-thiazolidine-2-ones

Several 5-arylidene-4-thioxo-thiazolidine-2-ones (3a-n) were synthesized and evaluated as antimicrobial agents against representative strains, including multidrug-resistant strains of clinical isolates. Also, the antiproliferative activity was evaluated against two human carcinoma cell lines (NCI-H292 and HEp-2). The compounds containing the 5-arylidene subunit presented greater antimicrobial activities against Gram positive bacteria, including the multidrug-resistant clinical isolates, than the 4-thioxo-thiazolidine-2-one. Important SAR information was also gathered, such as the contribution of thiocarbonyl attached at 4-position on the thiazolidine heterocyclic for antimicrobial properties. None of the derivatives exhibited significant antiproliferative activity against the human carcinoma cell lines.

Induction of cancer cell death by apoptosis and slow release of 5-fluoracil from metal-organic frameworks Cu-BTC.

This study aimed to evaluate the mechanism associated with cytotoxic activity displayed by the drug 5-fluorouracil incorporated in Cu-BTC MOF and its slow delivery from the Cu-BTC MOF. Structural characterization encompasses elemental analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction (XRD) was performed to verify the process of association between the drug 5-FU and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the mechanism responsible for the cell death. The release profile of the drug 5-FU from Cu-BTC MOF for 48 hours was obeisant. Also, the anti-inflammatory activity was evaluated by the peritonitis testing and the production of nitric oxide and pro-inflammatory cytokines were measured. The chemical characterization of the material indicated the presence of drug associated with the coordination network in a proportion of 0.82 g 5-FU per 1.0 g of Cu-BTC MOF. The cytotoxic tests were carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC MOF associated drug was extremely cytotoxic against the human breast cancer adenocarcinoma (MCF-7) cell line and against human acute promyelocytic leukemia cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug demonstrated a slow release profile where 82% of the drug was released in 48 hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased significantly the number of leukocytes in the peritoneal cavity of rodents as well as reduced levels of cytokines and nitric oxide production.

Synthesis and cytotoxic profile of glycosyl–triazole linked to 1,2,4-oxadiazole moiety at C-5 through a straight-chain carbon and oxygen atoms

The convergent synthesis of an unusual (but simple) class of compounds 5a-g has been achieved by the copper-catalyzed [3+2] cycloaddition reaction of 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide 4 with propynyl 3-[3-(aryl)-1,2,4-oxadiazol-5-yl] propionates 3a-g. The formerly known azide 4 has been prepared according to the literature procedure; however, the synthesis of esters 3a-g is being reported for the first time. The infrared as well as (1)H NMR spectra of all new products are in agreement with their proposed structures. By carrying out the nOe experiment of one of the final compounds 5a, we have been able to establish that only the 1,4-regioisomers have been formed in the cycloaddition reaction. All final products presented weak cytotoxic activity, but 5e and 5g had somewhat better behaviour showing 22-25% cell growth inhibition against two cell strains: NCI-H(292) (lung carcinoma) and HEp-2 (larynx carcinoma).

Does LLLT stimulate laryngeal carcinoma cells? An "in vitro" study

Low level laser therapy (LLLT) has been used successfully in biomedicine and some of the results are thought to be related to cell proliferation. The effects of LLLT on cell proliferation is debatable because studies have found both an increase and a decrease in proliferation of cell cultures. Cell culture is an excellent method to assess both effects and dose of treatment. The aim of this study was to assess the effect of 635nm and 670 nm laser irradiation of H.Ep.2 cells in vitro using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). The cells were obtained from squamous cell carcinoma (SCC) of the larynx and were routinely processed from defrost to the experimental condition. Twenty-four hours after transplantation the cells were irradiated with doses ranging from 0.04 to 0.48J/cm2 for seven consecutive days (5 mW diode lasers: 635nm or 670 nm, beam cross-section approximately 1 mm) at local light doses between 0.04 and 0.48 J/cm2. The results showed that 635nm laser light did not significantly stimulate the proliferation of H.Ep.2 cells at doses of 0.04 J/cm2 to 0.48 J/cm2, However, 670nm laser irradiation led to an increased cell proliferation when compared to both control and 635nm irradiated cells. The best cell proliferation was found with 670nm laser irradiated cultures exposed to doses of doses of 0.04 to 0.48 J/cm2. We conclude that both dose and wavelength are factors that may affect cell proliferation of H.Ep.2 cells.

Indigofera suffruticosa: an alternative anticancer therapy.

Indigofera suffruticosa Mill (Fabeceae) occurs in the Northeast countryside and has intensive popular use in the treatment of infectious, inflammatory and other processes. The main aim of the present work was to investigate the cytotoxic and antitumor effects of aqueous extracts of leaves of I. suffruticosa obtained by infusion and maceration as well as to evaluate the toxicological properties. Aqueous extracts did not exhibit cytotoxicity against HEp-2 (human epidermoid cancer cell) cell lines by MTT method. From the aqueous extract by infusion, the toxicological assay showed low order of toxicity. The antitumor effect of aqueous extracts by infusion (64.53%) and maceration (62.62%) against sarcoma 180 in mice at a dose of 50 mg kg−1 (intraperitoneally), based on low order of toxicity was comparable to the control group, which showed 100% development. Considering the low order of toxicity and that it is highly effective in inhibiting growth of solid tumors, the aqueous extracts of leaves of I. suffruticosa may be used as an alternative anticancer agent.

Tropane Alkaloids from Erythroxylum caatingaePlowman

Three tropane alkaloids, 1–3, were isolated from Erythroxylum caatingae, i.e., 6β‐benzoyloxy‐3α‐[(4‐hydroxy‐3,5‐dimethoxybenzoyl)oxy]tropane (1), a new tropane alkaloid, along with the known alkaloids 3α,6β‐dibenzoyloxytropane (2) and 6β‐benzoyloxy‐3α‐[(3,4,5‐trimethoxybenzoyl)oxy]tropane (catuabine B; 3). Their structures were determined by 2D‐ (1H and 13C) NMR. By LC/ESI‐MS/MS analysis of the fractions of alkaloids 1–3, it was possible to detect five more alkaloids, 4–8, two of these, 4 and 8, possibly being new natural products. X‐Ray crystallography of the chloride derivate of 1, i.e., 6β‐benzoyloxy‐3α‐(4‐hydroxy‐3,5‐dimethoxybenzoyloxy)tropane hydrochloride (1a) confirmed the structure of 1. Cytotoxicity was tested against the cell lines HEp‐2, NCI‐H292, and KB for the MeOH extract and alkaloid 3, and antitumor activity was tested against Sarcoma 180 only for the MeOH extract.