Watermelon Reduces the Toxicity of Cisplatin Treatment in C57BL/6 Mice with Induced Melanoma.

An alternative to reduce the undesirable effects of antineoplastic agents has been the combination of classical treatments with nutritional strategies aimed at reducing systemic toxicity without decreasing the antitumor activity of already used drugs. Within this context, this study evaluated the possible reduction of toxicity when cisplatin treatment is combined with watermelon pulp juice supplementation in C57BL/6 mice with melanoma. Watermelon is a fruit rich in vitamins, minerals, proteins, lycopene, carotene, and xanthophylls, which has shown effectiveness in the treatment of cardiovascular diseases, weight loss, urinary infections, gout, hypertension, and mutagenicity. The following parameters were analyzed: animal survival, bone marrow genotoxicity, serum creatinine and urea, histopathological features of the tumor tissue, tumor weight and volume, and weight of non-tumor tissues (kidney, liver, spleen, heart, and lung). The results showed that watermelon had no antitumor effect but reduced the toxicity of cisplatin, as demonstrated by an increase in the number of bone marrow cells and a decrease in serum creatinine and urea levels. The data suggest that watermelon pulp juice can be an alternative for reducing the side effects of antineoplastic agents.

Ellagitannins from jabuticaba (Myrciaria jaboticaba) seeds attenuated inflammation, oxidative stress, aberrant crypt foci, and modulated gut microbiota in rats with 1,2 dimethyl hydrazine-induced colon carcinogenesis.

Since dietary factors are thought to be responsible for high colon cancer risk, we investigated the chemopreventive effect of jabuticaba seed extract (LJE) by administering yogurt with or without LJE against 1,2 dimethyl hydrazine (DMH)-induced colon carcinogenesis in rats. Results showed that LJE contained a total phenolic content of 57.16 g/100 g of seed extract in which 7.67 and 10.09 g/100 g represented total flavonoids and ellagitannins, respectively. LJE protected DNA and human LDL against induced in vitro oxidation, which was associated with the ellagitannin content and with the free-radical scavenging and reducing capacities. LJE alone had a non-clastogenicity/aneugenicity property, but in combination with cisplatin, it enhanced the chromosome aberrations in cancer cells. In colon cancer-induced rats, yogurt with or without LJE caused a reduction in pro-inflammatory parameters, decreased the RNA expression of antiapoptotic cytokines and increased the expression of proapoptotic cytokines. Moreover, LJE attenuated colon cancer initiation and progression by decreasing aberrant crypt foci and LJE recovered the gut microbiome. Together, this evidence suggests that LJE provides chemopreventive protection against colon cancer development by reducing inflammation and increasing proapoptotic pathways.

Genotoxic and Chemopreventive Effects of Vochysia divergens Leaves (Pantanal, Brazil).

The medicinal plant Vochysia divergens is a colonizing tree species of the Pantanal, a unique and little explored wetland region in Brazil. This species is used in folk medicine as syrups and teas to treat respiratory infections, digestive disorders, asthma, scarring, and skin diseases. The objectives of this study were to evaluate the antioxidant, cytotoxic, and genotoxic potential of the ethanolic extract of Vochysia divergens leaves (VdE), as well as the influence of VdE and its major component (the flavone 3',5-dimethoxy luteolin-7-O-ß-glucopyranoside; 3'5 DL) on MMS-induced genotoxicity. The extract significantly reduced the viability of V79 cells in the colorimetric XTT assay at concentrations ≥ 39 µg/mL. A significant increase in micronucleus frequencies was observed in V79 cell cultures treated with VdE concentrations of 160 and 320 µg/mL. However, animals treated with the tested doses of VdE (500, 1000, and 2000 mg/kg b.w.) exhibited frequencies that did not differ significantly from those of the negative control group, indicating the absence of genotoxicity. The results also showed that VdE was effective in reducing MMS-induced genotoxicity at concentrations of 20, 40, and 80 µg/mL in the in vitro test system and at a dose of 15 mg/kg b.w. in the in vivo test system. Its major component 3'5 DL exerted no protective effect, suggesting that it is not responsible for the effect of the extract. The results of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that VdE was able to scavenge 92.6% of free radicals. In conclusion, the results suggest that the protective effect of VdE may be related, at least in part, to the antioxidant activity of its chemical constituents.

Assessment of genotoxic activity of oleoresins and leaves extracts of six Copaifera species for prediction of potential human risks.

ETHNOPHARMACOLOGICAL RELEVANCE: Copaifera species are used in folk medicine for a wide variety of pharmacological properties. This paper reports the cytotoxic and genotoxic analyses of oleoresins and leaves extracts of Copaifera species: C. duckei, C. multijuga, C. paupera, C. pubiflora, C. reticulata and C. trapezifolia. MATERIALS AND METHODS: In vitro assays were performed using Chinese hamster lung fibroblasts (V79 cells). The clonogenic efficiency and cytokinesis-block micronucleus assays were employed for the cytotoxicity and genotoxicity assessment, respectively. The mouse bone marrow micronucleus test was used for in vivo studies. RESULTS: The cytotoxicity results using the clonogenic efficiency assay showed IC50 values ranging from 9.8 to 99.2 µg/mL for oleoresins and 66.4-721.5 for leaves extracts. However, no cytotoxic effect was observed in the in vivo studies. Additionally, the treatments with oleoresins and leaves extracts did not significantly increase the frequency of micronuclei in both in vitro and in vivo mammalian cells. The UPLC-MS/MS and CG/MS analyses of Copaifera oleoresins allowed the identification of 10 acid diterpenes and 11 major volatile sesquiterpenes. Leaves are rich in phenolic compounds including two flavonoid heterosides and 16 galloylquinic acid derivatives. CONCLUSIONS: The oleoresins and leaves extracts of studied Copaifera species were not cytotoxic in vivo, as well as not genotoxic in both in vitro and vivo assays, under the experimental conditions used. Therefore, the obtained results should be sufficient to demonstrate the absence of significant genotoxic risk of these Copaifera products for human use in the evaluated concentrations range.

Europium(III)-doped yttrium vanadate nanoparticles reduce the toxicity of cisplatin.

The aim of this study was to evaluate the antitumor efficiency of chemotherapy with cisplatin alone and incorporated into europium(III)-doped yttrium vanadate nanoparticles functionalized with 3­chloropropyltrimethoxysilane with folic acid and without folic acid in a syngeneic mouse melanoma model. Histopathological, biochemical and genotoxic analyses of treated animals were performed to assess the toxicity of treatments. The treatment of the animals with cisplatin alone and the nanoparticles functionalized with cisplatin at a dose of 5 mg/kg b.w. for 5 days reduced tumor weight about 86% and 65%, respectively. Histopathological analysis showed lower mean frequency of mitoses in tumor tissue of the groups receiving cisplatin alone (90% reduction) and the nanoparticles functionalized with cisplatin (70% reduction) compared to the tumor control group. A reduction in body and liver weight and an increase in serum creatinine and urea levels were observed in animals treated with CDDP, but not in those receiving the nanoparticles functionalized with cisplatin. Genotoxicity assessment by the comet assay revealed lower frequencies of DNA damage in animals treated with the nanoparticles functionalized with cisplatin (mean score = 140.80) compared to those treated with cisplatin alone (mean score = 231.80). Marked toxic effects were observed in animals treated with cisplatin alone, while treatment with the nanoparticles functionalized with cisplatin showed no toxicity. Moreover, folic acid in the inorganic nanoparticles reduced the genotoxicity of cisplatin in the bone marrow micronucleus test (10 ±â€¯1.4 and 40 ±â€¯0.0 micronucleus, respectively). These results demonstrate the antitumor efficiency and significantly reduced systemic toxicity of the nanoparticles compared to CDDP.

Toxicogenetic study of Persea americana fruit pulp oil and its effect on genomic instability.

Persea americana Mill., commonly known as avocado, is a tree native to Central America that is widely used as a food source and for the treatment of diseases. This plant has various biological properties such as analgesic, anti-inflammatory and total cholesterol-lowering activity. In view of its pharmacological potential, we conducted a toxicogenetic study of the fruit pulp oil of P. americana (PAO) and investigated its influence on genotoxicity induced by methyl methanesulfonate (MMS) and doxorubicin. V79 cells and Swiss mice were used for the assays. The results showed no genotoxic effects of PAO in the in vitro or in vivo test systems. However, the highest PAO dose tested led to an increase in the levels of aspartate aminotransferase, indicating hepatic/tissue damage. This effect may be related to high concentrations of palmitic acid, the main component of PAO. Furthermore, PAO was effective in reducing the chromosome damage induced by MMS and doxorubicin. These results contribute to the safety assessment of PAO as a medicinal plant for human use.

Influence of Styrax camporum and of Chemical Markers (Egonol and Homoegonol) on DNA Damage Induced by Mutagens with Different Mechanisms of Action.

This study evaluated the influence of Styrax camporum stems hydroalcoholic extract (SCHE) and of chemical markers of the genus, egonol (EG) and homoegonol (HE), on DNA damage induced in V79 cells by mutagens with different mechanisms of action. These natural products were combined with different mutagens [methyl methanesulfonate (MMS), hydrogen peroxide (H2O2), (S)-(+)-camptothecin (CPT), and etoposide (VP-16)] to evaluate the modulatory effect on DNA damage. The results showed that SCHE was genotoxic at the highest concentration tested (60 µg/mL). Treatment with EG or HE alone induced no genotoxic effect, while genotoxic activity was observed when the two compounds were combined. The SCHE extract was able to reduce the frequency of micronuclei induced by H2O2 and VP-16. Similar results were observed when the cell cultures were treated with EG and/or HE plus VP-16. In contrast, the highest concentration (40 µg/mL) SCHE potentiated DNA damage induced by VP-16. Neolignan EG alone or combined with HE also potentiated H2O2-induced genotoxicity. However, these natural products did not influence the frequency of DNA damage induced by MMS or CPT. Therefore, the influence of SCHE and of chemical markers (EG and HE) of the genus on the induction of DNA damage depends on the concentration tested and on the mutagen used.

Assessment of the antibacterial, cytotoxic and mutagenic potential of the phenolic-rich hydroalcoholic extract from Copaifera trapezifolia Hayne leaves.

Copaifera trapezifolia Hayne occurs in the Atlantic Rainforest, which is considered one of the most important and endangered tropical forests on the planet. Although literature works have described many Copaifera spp., their biological activities remain little known. In the present study, we aimed to evaluate (1) the potential of the hydroalcoholic extract from C. trapezifolia leaves (CTE) to act against the causative agents of tooth decay and apical periodontitis and (2) the cytotoxicity and mutagenicity of CTE to ensure that it is safe for subsequent application. Concerning the tested bacteria, the MIC and the minimum bactericidal concentration of CTE varied between 100 and 400 µg ml-1. The time-kill assay conducted at a CTE concentration of 100 µg ml-1 evidenced bactericidal activity against Porphyromonas gingivalis (ATCC 33277) and Peptostreptococcus micros (clinical isolate) within 72 h. CTE at 200 µg ml-1 inhibited Porphyromonas gingivalis and Peptostreptococcus micros biofilm formation by at least 50 %. A combination of CTE with chlorhexidine dichlorohydrate did not prompt any synergistic effects. The colony-forming assay conducted on V79 cells showed that CTE was cytotoxic at concentrations above 156 µg ml-1. CTE exerted mutagenic effect on V79 cells, but the micronucleus test conducted on Swiss mice and the Ames test did not reveal any mutagenicity. Therefore, the use of standardized and safe extracts could be an important strategy to develop novel oral care products with antibacterial action. These extracts could also serve as a source of compounds for the discovery of new promising biomolecules.

Antigenotoxic and Antioxidant Properties of Solanum cernuum and Its Alkaloid, Cernumidine.

Solanum cernuum VE. has been used extensively for the treatment of urinary disorders, gonorrhea and skin infections; cernumidine is a major component of S. cernuum (SC) hydroalcoholic extract. The micronucleus test in V79 cells was used to evaluate the genotoxic and antigenotoxic potential of SC and cernumidine. For antigenotoxicity assessment, methyl methanesulfonate (MMS, 44 µg/mL) and hydrogen peroxide (H2O2, 3.5 µg/mL) were added as inducers of chromosome damage. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Significantly higher frequencies of micronuclei were observed in cell cultures treated with SC concentrations of 160 and 320 µg/mL in comparison with the negative control, demonstrating a genotoxic effect. There was no significant difference in the frequency of micronuclei between cell cultures treated with a combination of SC and MMS and those treated only with MMS. On the other hand, a significant reduction in the frequency of micronuclei was observed for V79 cells treated with SC or cernumidine plus H2O2 compared to those treated only with H2O2. Furthermore, SC and cernumidine were able to scavenge free radicals in the DPPH assay. Thus, the protective effect of SC and cernumidine against H2O2 can be attributed to antioxidant activity.

Modulatory Effect of Betulinic Acid on the Genotoxicity Induced by Different Mutagens in V79 Cells.

Betulinic acid (BA) is a pentacyclic triterpene that can be isolated from many medicinal plants around the world. The aim of this study was to evaluate the genotoxic potential of BA and its effect on the genotoxicity induced by different mutagens in V79 cells using the cytokinesis-block micronucleus assay. Different BA concentrations were combined with methyl methanesulfonate (MMS), doxorubicin (DXR), camptothecin (CPT), and etoposide (VP-16). The frequencies of micronuclei in cultures treated with different BA concentrations did not differ from those of the negative control. Treatment with BA and MMS resulted in lower micronucleus frequencies than those observed for cultures treated with MMS alone. On the other hand, a significant increase in micronucleus frequencies was observed in cultures treated with BA combined with DXR or VP-16 when compared to these mutagens alone. The results showed no effect of BA on CPT-induced genotoxicity. Therefore, BA was not genotoxic under the present experimental conditions and exerted a different influence on the genotoxicity induced by different mutagens. The modulatory effect of BA depends on the type of mutagen and concentrations used.

Copaifera reticulata oleoresin: Chemical characterization and antibacterial properties against oral pathogens.

Oral infections such as periodontitis and tooth decay are the most common diseases of humankind. Oleoresins from different copaifera species display antimicrobial and anti-inflammatory activities. Copaifera reticulata is the commonest tree of this genus and grows abundantly in several Brazilian states, such as Pará, Amazonas, and Ceará. The present study has evaluated the chemical composition and antimicrobial potential of the Copaifera reticulata oleoresin (CRO) against the causative agents of tooth decay and periodontitis and has assessed the CRO cytotoxic potential. Cutting edge analytical techniques (GC-MS and LC-MS) aided the chemical characterization of CRO. Antimicrobial assays included determination of the Minimum Inhibitory Concentration (MIC), determination of the Minimum Bactericidal Concentration (MBC), determination of the Minimum Inhibitory Concentration of Biofilm (MICB50), Time Kill Assay, and Checkerboard Dilution. Conduction of XTT assays on human lung fibroblasts (GM07492-A cells) helped to examine the CRO cytotoxic potential. Chromatographic analyses revealed that the major constituents of CRO were ß-bisabolene, trans-α-bergamotene, ß-selinene, α-selinene, and the terpene acids ent-agathic-15-methyl ester, ent-copalic acid, and ent-polyalthic acid. MIC and MBC results ranged from 6.25 to 200 µg/mL against the tested bacteria. The time-kill assay conducted with CRO at concentrations between 50 and 100 µg/mL showed bactericidal activity against Fusobacterium nucleatum (ATCC 25586) and Streptococcus mitis (ATCC 49456) after 4 h, Prevotella nigrescens (ATCC 33563) after 6 h, Porphyromonas gingivalis (ATCC 33277) and Lactobacillus casei (clinical isolate) after 12 h, and Streptococcus salivarius (ATCC 25975) and Streptococcus mutans (ATCC 25175) after 18 h. The fractional inhibitory concentration indexes (FICIs) revealed antagonistic interaction for Lactobacillus casei (clinical isolate), indifferent effect for Porphyromonas gingivalis (ATCC 33277), Fusobacterium nucleatum (ATCC 25586), Prevotella nigrescens (ATCC 33563), and Streptococcus salivarius (ATCC 25975), and additive effect for Streptococcus mutans (ATCC 25175) and Streptococcus mitis (ATCC 49456). Treatment of GM07492-A cells with CRO demonstrated that concentrations up to 39 µg/mL significantly reduced cell viability as compared to the negative control, being IC50 equal to 51.85 ± 5.4 µg/mL. These results indicated that CRO plays an important part in the search for novel sources of agents that can act against oral pathogens.

Study of the cytotoxic activity of Styrax camporum extract and its chemical markers, egonol and homoegonol.

The benzofuran lignans egonol and homoegonol are found in all species of the genus Styrax. Since natural products are important sources of new anticancer drugs, this study evaluated the cytotoxic activity of a hydroalcoholic extract of the stems of S. camporum (SCHE) and their chemical markers, egonol (EG) and homoegonol (HE), against different tumor cell lines (B16F10, MCF-7, HeLa, HepG2, and MO59J). A normal human cell line (GM07492A) was included. Cytotoxic activity was evaluated at different treatment times (24, 48 and 72 h) using the XTT assay. More effective results were observed after 72 h of treatment. The lowest IC50 values were found for the HepG2 cell line, ranging from 11.2 to 55.0 µg/mL. The combination of EG and HE exerted higher cytotoxic activity than SCHE or treatment with either lignan alone, with the lowest IC50 (13.31 µg/mL) being observed for the MCF-7 line. Furthermore, treatment with these lignans was significantly more cytotoxic for some tumor cell lines compared to the normal cell line, GM07492A, indicating selectivity. These results suggest that these lignans may be used to treat cancer without affecting normal cells.

Manool, a Salvia officinalis diterpene, induces selective cytotoxicity in cancer cells.

Manool, a diterpene isolated from Salvia officinalis, was evaluated by the XTT colorimetric assay for cytotoxicity and selectivity against different cancer cell lines: B16F10 (murine melanoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), HepG2 (human hepatocellular carcinoma), and MO59J, U343 and U251 (human glioblastoma). A normal cell line (V79, Chinese hamster lung fibroblasts) was used to compare the selectivity of the test substance. Manool exhibited higher cytotoxic activity against HeLa (IC50 = 6.7 ± 1.1 µg/mL) and U343 (IC50 = 6.7 ± 1.2 µg/mL) cells. In addition, in the used experimental protocols, the treatment with manool was significantly more cytotoxic for different tumor cell lines than for the normal cell line V79 (IC50 = 49.3 ± 3.3 µg/mL), and showed high selectivity. These results suggest that manool may be used to treat cancer without affecting normal cells.

Synthesis and evaluation of antibacterial and antitumor activities of new galactopyranosylated amino alcohols.

Three series of d-galactose derivatives linked to a lipophilic aminoalcohol moiety were synthesized and their antibacterial activity was evaluated against Mycobacterium tuberculosis and representative species of Gram positive and Gram negative bacteria. Five out of the thirteen tested compounds displayed activity against M. tuberculosis, with a minimal inhibitory concentration (MIC) of 12.5 µg/mL and seven compounds were active against the four bacterial strains tested. The best results were obtained for amino alcohols 10 and 11 against Staphylococcus epidermidis (MIC = 2 µg/mL). The antitumor activity was evaluated against three tumor cell lines (MCF-7, HeLa and MO59J) and compared to the normal cell line GM07492A. The results showed that the lowest IC50 values were observed for the amino alcohol 16 against MCF-7 (11.9 µM) and MO59J (10.0 µM).

Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates.

Novel gold(I) and gold(III) complexes containing derivatives of D-galactose, D-ribose and D-glucono-1,5-lactone as ligands were synthesized and characterized by IR, (1)H, and (13)C NMR, high resolution mass spectra and cyclic voltammetry. The compounds were evaluated in vitro for their cytotoxicity against three types of tumor cells: cervical carcinoma (HeLa) breast adenocarcinoma (MCF-7) and glioblastoma (MO59J) and one non-tumor cell line: human lung fibroblasts (GM07492A). Their antitubercular activity was evaluated as well expressed as the minimum inhibitory concentration (MIC90) in µg/mL. In general, the gold(I) complexes were more active than gold(III) complexes, for example, the gold(I) complex (1) was about 8.8 times and 7.6 times more cytotoxic than gold(III) complex (8) in MO59J and MCF-7 cells, respectively. Ribose and alkyl phosphine derivative complexes were more active than galactose and aryl phosphine complexes. The presence of a thiazolidine ring did not improve the cytotoxicity. The study of the cytotoxic activity revealed effective antitumor activities for the gold(I) complexes, being more active than cisplatin in all the tested tumor cell lines. Gold(I) compounds (1), (2), (3), (4) and (6) exhibited relevant antitubercular activity even when compared with first line drugs such as rifampicin.

Preparation and characterization of a bacterial cellulose/silk fibroin sponge scaffold for tissue regeneration.

Bacterial cellulose (BC) and silk fibroin (SF) are natural biopolymers successfully applied in tissue engineering and biomedical fields. In this work nanocomposites based on BC and SF were prepared and characterized by scanning electron microscopy (SEM), infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). In addition, the investigation of cytocompatibility was done by MTT, XTT and Trypan Blue dye technique. Cellular adhesion and proliferation were detected additionally. The evaluation of genotoxicity was realized by micronucleus assay. In vitro tests showed that the material is non-cytotoxic or genotoxic. SEM images revealed a greater number of cells attached at the BC/SF:50% scaffold surface than the pure BC one, suggesting that the presence of fibroin improved cell attachment. This could be related to the SF amino acid sequence that acts as cell receptors facilitating cell adhesion and growth. Consequently, BC/SF:50% scaffolds configured an excellent option in bioengineering depicting its potential for tissue regeneration and cultivation of cells on nanocomposites.

In vivo assessment of genotoxic, antigenotoxic and anticarcinogenic activities of Solanum lycocarpum fruits glycoalkaloidic extract.

The fruits of Solanum lycocarpum, known as wolf-fruit, are used in folk medicine, and because of that we have evaluated both the genotoxic potential of its glycoalkaloidic extract (SL) and its influence on the genotoxicity induced by methyl methanesulfonate. Furthermore, the potential blocking effect of SL intake in the initial stage of colon carcinogenesis in Wistar rats was investigated in a short-term (4-week) bioassay using aberrant crypt foci (ACF) as biomarker. The genotoxic potential was evaluated using the Swiss mice peripheral blood micronucleus test. The animals were treated with different doses of SL (15, 30 and 60 mg/kg b.w.) for 14 days, and the peripheral blood samples were collected at 48 h, 7 days and 14 days after starting the treatment. For antigenotoxicity assessment, MMS was administered on the 14th day, and after 24 h the harvesting of bone marrow and liver cells was performed, for the micronucleus and comet assays, respectively. In the ACF assay, male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg b.w.), twice a week, during two weeks to induce ACF. The treatment with SL (15, 30 and 60 mg/kg b.w.) was given for four weeks during and after carcinogen treatment to investigate the potential beneficial effects of SL on DMH-induced ACF. The results demonstrated that SL was not genotoxic in the mouse micronucleus test. In animals treated with SL and MMS, the frequencies of micronucleus and extensions of DNA damage were significantly reduced in comparison with the animals receiving only MMS. Regarding the ACF assay, SL significantly reduced the frequency of ACF induced by DMH.

Differential effect of manool--a diterpene from Salvia officinalis, on genotoxicity induced by methyl methanesulfonate in V79 and HepG2 cells.

Salvia officinalis (sage) is a perennial woody subshrub native to the Mediterranean region that is commonly used as a condiment and as an anti-inflammatory, antioxidant and antimicrobial agent due to its biological activities. Manool is the most abundant micro-metabolite found in Salvia officinalis essential oils and extracts. We therefore decided to evaluate the cytotoxic, genotoxic and antigenotoxic potential of manool in Chinese hamster lung fibroblasts (V79) and human hepatoma cells (HepG2). Cytotoxicity was assessed by the colony-forming assay in V79 cells and toxic effects were observed at concentrations of up to 8.0 µg/mL. The micronucleus test was used to evaluate the genotoxicity and antigenotoxicity of manool in V79 and HepG2 cells at concentrations of 0.5-6.0 µg/mL and 0.5-8.0 µg/mL, respectively. For evaluation of antigenotoxicity, the concentrations of manool were combined with methyl methanesulfonate (MMS, 44 µg/mL). The results showed a significant increase in the frequency of micronuclei in cultures of both cell lines treated with the highest concentration tested, demonstrating a genotoxic effect. On the other hand, manool exhibited a protective effect against chromosome damage induced by MMS in HepG2 cells, but not in V79 cells. These data suggest that some manool metabolite may be responsible for the antigenotoxic effect observed in HepG2 cells.

Comparative evaluation of antiproliferative effects of Brazilian green propolis, its main source Baccharis dracunculifolia, and their major constituents artepillin C and baccharin.

This study evaluated the antiproliferative activity of the Brazilian green propolis and Baccharis dracunculifolia extracts and their major compounds artepillin C and baccharin in different tumor cell lines. The lowest IC50 values observed for Brazilian green propolis and B. dracunculifolia extracts were 41.0 ± 4.5 µg/mL for U343 and 44.9 ± 7.1 µg/mL for HepG2, respectively. Regarding artepillin C and baccharin, the lowest IC50 values were 20.1 ± 2.9 for U343 and 13.0 ± 1.5 µg/mL for B16F10, respectively. For the association of artepillin C plus baccharin, the lowest IC50 result was 35.2 ± 0.5 µg/mL for B16F10. Artepillin C and baccharin were more cytotoxic than both Brazilian green propolis and B. dracunculifolia extracts. No additive or synergistic effect was observed for the association of artepillin C plus baccharin.

Antiproliferative activity of Solanum lycocarpum alkaloidic extract and their constituents, solamargine and solasonine, in tumor cell lines.

Natural products are some of the important sources of new anticancer drugs. The Brazilian flora is considered one of the most diverse in the word, although not many large-scale pharmacological and phytochemical studies have been conducted to date. With this in mind, in the present study we evaluated the antiproliferative activity of Solanum lycocarpum fruit glycoalkaloid extract (SL) and its major compounds, solamargine (SM) and solasonine (SS), against different tumor cell lines: murine melanoma (B16F10), human colon carcinoma (HT29), human breast adenocarcinoma (MCF-7), human cervical adenocarcinoma (HeLa), human hepatocellular liver carcinoma (HepG2) and human glioblastoma (MO59J, U343 and U251). The antiproliferative activity was evaluated using XTT assay and results were expressed as IC50. The most pronounced antiproliferative activity was observed for SM, with IC50 values ranging from 4.58 to 18.23 µg/mL. The lowest IC50 values were observed against HepG2, being 9.60 µg/mL for SL, 4.58 µg/mL for SM and 6.01 µg/mL for SS. Thus, SL, SM and SS demonstrated antiproliferative activity against the tumor cell lines tested, and were most effective against the HepG2 cell line.