Anderson Junger Teodoro

Effect of lycopene on cell viability and cell cycle progression in human cancer cell lines

BackgroundLycopene, a major carotenoid component of tomato, has a potential anticancer activity in many types of cancer. Epidemiological and clinical trials rarely provide evidence for mechanisms of the compound’s action, and studies on its effect on cancer of different cell origins are now being done. The aim of the present study was to determine the effect of lycopene on cell cycle and cell viability in eight human cancer cell lines.MethodsHuman cell lines were treated with lycopene (1–5 μM) for 48 and 96 h. Cell viability was monitored using the method of MTT. The cell cycle was analyzed by flow cytometry, and apoptotic cells were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick labeling (TUNEL) and by DAPI.ResultsOur data showed a significant decrease in the number of viable cells in three cancer cells lines (HT-29, T84 and MCF-7) after 48 h treatment with lycopene, and changes in the fraction of cells retained in different cell cycle phases. Lycopene promoted also cell cycle arrest followed by decreased cell viability in majority of cell lines after 96 h, as compared to controls. Furthermore, an increase in apoptosis was observed in four cell lines (T-84, HT-29, MCF-7 and DU145) when cells were treated with lycopene.ConclusionsOur findings show the capacity of lycopene to inhibit cell proliferation, arrest cell cycle in different phases and increase apoptosis, mainly in breast, colon and prostate lines after 96 h. These observations suggest that lycopene may alter cell cycle regulatory proteins depending on the type of cancer and the dose of lycopene administration. Taken together, these data indicated that the antiproliferative effect of lycopene was cellular type, time and dose-dependent.

Influence of Lycopene on Cell Viability, Cell Cycle, and Apoptosis of Human Prostate Cancer and Benign Hyperplastic Cells

Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related mortality in men of the Western world. Lycopene has received attention because of its expcted potential to prevent cancer. In the present study, we evaluated the influence of lycopene on cell viability, cell cycle, and apoptosis of human prostate cancer cells and benign prostate hyperplastic cells. Using MTT assay, we observed a decrease of cell viability in all cancer cell lines after treatment with lycopene, which decreased the percentage of cells in G0/G1 phase and increased in S and G2/M phases after 96 h of treatment in metastatic prostate cancer cell lineages. Flow citometry analysis of cell cycle revealed lycopene promoted cell cycle arrest in G0/G1 phase after 48 and 96 h of treatment in a primary cancer cell line. Using real time PCR assay, lycopene also induced apoptosis in prostate cancer cells with altered gene expression of Bax and Bcl-2. No effect was observed in benign prostate hyperplasia cells. These results suggest an effect of lycopene on activity of human prostate cancer cells.

Lycopene and Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells

Pituitary adenomas comprise approximately 10–15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing’s disease.

Silymarin Reduces Profibrogenic Cytokines and Reverses Hepatic Fibrosis in Chronic Murine Schistosomiasis

ABSTRACT In chronic schistosomiasis, hepatic fibrosis is linked to the portal hypertension that causes morbidity in Schistosoma mansoni infection. Silymarin (SIL) is a hepatoprotective and antioxidant medicament largely prescribed against liver diseases that has previously been shown to prevent fibrosis during acute murine schistosomiasis. Here we employed silymarin to try to reverse established hepatic fibrosis in chronic schistosomiasis. Silymarin or vehicle was administered to BALB/c mice every 48 h, starting on the 40th (80 days of treatment), 70th (50 days), or 110th (10 days) day postinfection (dpi). All mice were sacrificed and analyzed at 120 dpi. Treatment with silymarin reduced liver weight and granuloma sizes, reduced the increase in alanine aminotransferase and aspartate aminotransferase levels, and reduced the established hepatic fibrosis (assessed by hydroxyproline contents and picrosirius staining). Treatment with silymarin also reduced the levels of interleukin-13 (IL-13) in serum and increased the gamma interferon (IFN-γ)/IL-13 ratio. There was a linear correlation between IL-13 levels in serum and hydroxyproline hepatic content in both infected untreated and SIL-treated mice, with decreased IL-13 levels corresponding to decreased hydroxyproline hepatic contents. Treatment with either SIL or N-acetylcysteine reduced both proliferation of fibroblast cell lines and basal/IL-13-induced production of collagen I, indicating that besides inhibiting IL-13 production during infection, SIL antioxidant properties most likely contribute to inhibition of collagen production downstream of IL-13. These results show that silymarin interferes with fibrogenic cytokines, reduces established fibrosis, and inhibits downstream effects of IL-13 on fibrogenesis, indicating the drug as a safe and cheap treatment to liver fibrotic disease in schistosomiasis.

Antioxidant Activity and Cytotoxicity Effect of Cocoa Beans Subjected to Different Processing Conditions in Human Lung Carcinoma Cells

Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1 phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer.

Determinação dos teores de zinco em diferentes extratos de hortaliças dos tipos A e B

O zinco e um elemento traco essencial as diversas funcoes bioquimicas do organismo humano. As interacoes fisico-quimicas entre nutrientes incluem: adsorcao, formacao de complexos e precipitacao, influenciando na biodisponibilidade. Atraves da determinacao do teor total do metal ingerido, nao e possivel medir o quanto deste metal sera absorvido. Entretanto, atraves da tecnica de especiacao dos metais, que e definida como a determinacao da concentracao das formas fisico-quimicas individuais dos elementos que, em conjunto, constitua a concentracao total do mesmo na amostra, podemos ter novos dados para prever sua absorcao. Para a especiacao em amostras solidas, inicialmente deve ser aplicado um metodo de extracao sequencial ou seletivo. Amostras de hortalicas dos tipos A e B foram analisadas quanto ao teor total de zinco atraves de espectroscopia de absorcao atomica em chama, e o metodo de extracao sequencial foi aplicado com os seguintes extratores: solucao de CaCl2 1M; solucao de acido acetico 0,1M; solucao de acido acetico 0,5M/acetato de amonio 5% [pH=5,0]; solucao de NaOH 0,1M e solucao de HCl 0,5M. Na analise da rejeicao de resultados foi aplicado o teste de Grubbs. Em 8 amostras a extracao do zinco foi considerada total, 6 amostras apresentaram extracao superior a 75%, 5 amostras extracao de 50% , amostra de quiabo teve 27% do total de zinco extraido e amostra de beterraba apenas 3%. Observa-se que para a maioria das amostras, o zinco se encontra sob a forma de no minimo 6 especies quimicas distintas. Estudos posteriores, que permitam a identificacao destas especies, favorecera a avaliacao da biodisponibilidade deste metal.

Chemical, sensory, and functional properties of whey-based popsicles manufactured with watermelon juice concentrated at different temperatures

The effects of the concentration of watermelon juice at different temperatures (45, 55, or 65 °C) on the physicochemical and sensory characteristics, antioxidant capacity, and volatile organic compounds (VOCs) of whey-based popsicles were investigated. Total phenolic content, lycopene, citrulline, VOCs, melting rate, instrumental colour, antioxidant capacity, and the sensory characteristics (hedonic test and free listing) were determined. The temperature led to a significant decrease in bioactive compounds (total phenolics, lycopene, and citrulline). The popsicle manufactured with reconstituted watermelon juice concentrated to 60 °Brix at 65 °C presented higher antioxidant capacity and was characterized by the presence of alcohols, aldehydes and ketones and presented a similar acceptance to the untreated popsicle (except for flavour). It is possible to combine whey and concentrated watermelon juice for the manufacture of bioactive-rich popsicles, using the concentration temperature of 65 °C as a suitable processing condition for potential industrial applications.

Determinação dos teores de cobre em diferentes extratos de hortaliças do tipo A e B

O zinco e um elemento traco essencial as diversas funcoes bioquimicas do organismo humano. As interacoes fisico-quimicas entre nutrientes incluem: adsorcao, formacao de complexos e precipitacao, influenciando na biodisponibilidade. Atraves da determinacao do teor total do metal ingerido, nao e possivel medir o quanto deste metal sera absorvido. Entretanto, atraves da tecnica de especiacao dos metais, que e definida como a determinacao da concentracao das formas fisico-quimicas individuais dos elementos que, em conjunto, constitua a concentracao total do mesmo na amostra, podemos ter novos dados para prever sua absorcao. Para a especiacao em amostras solidas, inicialmente deve ser aplicado um metodo de extracao sequencial ou seletivo. Amostras de hortalicas dos tipos A e B foram analisadas quanto ao teor total de zinco atraves de espectroscopia de absorcao atomica em chama, e o metodo de extracao sequencial foi aplicado com os seguintes extratores: solucao de CaCl2 1M; solucao de acido acetico 0,1M; solucao de acido acetico 0,5M/acetato de amonio 5% [pH=5,0]; solucao de NaOH 0,1M e solucao de HCl 0,5M. Na analise da rejeicao de resultados foi aplicado o teste de Grubbs. Em 8 amostras a extracao do zinco foi considerada total, 6 amostras apresentaram extracao superior a 75%, 5 amostras extracao de 50% , amostra de quiabo teve 27% do total de zinco extraido e amostra de beterraba apenas 3%. Observa-se que para a maioria das amostras, o zinco se encontra sob a forma de no minimo 6 especies quimicas distintas. Estudos posteriores, que permitam a identificacao destas especies, favorecera a avaliacao da biodisponibilidade deste metal.

Lycopene Extracts from Different Tomato-Based Food Products Induce Apoptosis in Cultured Human Primary Prostate Cancer Cells and Regulate TP53, Bax and Bcl-2 Transcript Expression

Carotenoids are the main tomato components, especially lycopene. Lycopene is more bioavailable in tomato processed products than in raw tomatos, since formation of lycopene cis-isomers during food processing and storage may increase its biological activity. In the current study, we evaluated the influence of lycopene extracts (5 mg / mL) from different tomato-based food products (paste, sauce, extract and ketchup) on cell viability and apoptosis on primary human prostate cancer cells (PCa cels) for 96h. Using MTT assay, we observed a significant decrease on primary PCa cell viability upon treatment with lycopene extracted from either 4 tomato-based food products. Flow cytometeric analysis revealed that lycopene from tomato extract and tomato sauce promoted up to fifty-fold increase on the proportion of apoptotic cells, when compared to the control group. Using real time PCR assay, we found that lycopene promoted an upregulation of TP53 and Bax transcript expression and also downregulation of Bcl-2 expression in PCa cells. In conclusion, our data demostrate that cis-lycopene promoted a significant inhibition on primary PCa cell viability, as well as an increase on their apoptotic rates, evidencing that cis-lycopene contained in tomato sauce and extract cain mainly modulate of primary human prostate cancer cell survival.

Anticancer properties of bioactive compounds of berry fruits - a review.

An overwhelming body of research has now firmly established that the dietary intake of berry fruits has a positive and profound impact on human health, performance, and disease. Evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. Studies show that the anticancer effects of berry bioactives reduce and repair damage resulting from oxidative stress and inflammation. In addition, also regulate carcinogen and xenobiotic metabolizing enzymes, various transcriptions and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and consumption may provide protection from therapy-associated toxicities. This paper is a comprehensive review of the effects of phytochemicals present in berry fruits on cancer and encompasses the occurrence and bioavailability of these compounds evidences for their effects on the various mechanisms by which may exert their effects. These include effects on cellular differentiation and apoptosis; effects on proteins and enzymes that are involved in these processes Review Article Castro and Teodoro; BJMMR, 6(8): 771-794, 2015; Article no.BJMMR.2015.252 772 at a molecular level, and other various effects through altered immune function and chemical metabolism.