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Ethnopharmacological relevance Casearia sylvestris is a tree found in tropical America. In Brazil it is known mainly as Guaçatonga. Literature reports suggest that the leaves and other plant parts have been used by indigenous populations from South America in preparations, mainly aqueous or hydroethanolic macerations or decoctions, most times taken orally for the primary treatment of several diseases, including cancer. Aim of the study This article reports the results of an investigation about the antiproliferative effects of Casearia sylvestris on tumor cells in vitro and in vivo . Material and methods Aqueous ethanolic maceration and column chromatography were done to obtain a crude aqueous ethanolic extract (CAE) and a chloroform fraction (f-CHCl 3 ). The human breast cancer cell line MCF-7 was used in culture. In vitro , non-cytotoxic concentrations were determined by MTT assay and the antiproliferative effect was assessed by the colony forming unit assay using non-cytotoxic concentrations. Effects on the cell cycle were observed through flow cytometry using a propidium iodide kit. Casearin C was identified in f-CHCl 3 by chromatography and H 1 nuclear magnetic resonance. The effect on some key proteins of DNA damage (phosphorylation on the histone H2AX) and cell cycle control (p53, p16, cdk2) was evaluated through immunoblot. Antiproliferative effects in vivo were measured in tumor tissue from Ehrlich ascites-bearing mice through the 3 H-thymidine uptake assay and the trypan blue exclusion method. Results In vitro , EC 50 values found at 24 h on MCF-7 cells were 141 µg/mL for CAE and 66 µg/mL for f-CHCl 3 . Inhibition on proliferation was recorded at concentrations as low as 4 µg/mL in the case of the f-CHCl 3 (up to 40%) and up to 50% when CAE was added at 9 µg/mL. The cell cycle arrest was demonstrated by the reduction in terms of number of cells in phases G2/M and S, up to 38.9% and 51.9% when cells were treated with CAE, and 53.9% and 66.2%, respectively, when cells were treated with f-CHCl 3 . The number of cells in G1 was increased when the cells were treated with CAE (21.4%) or f-CHCl 3 (27.8%). Key proteins of cell cycle control were affected. The treatments caused activation of p53, p16 and DNA damage found by the appearance of bands corresponding to γ -H2AX. The treatments caused inhibition of cdk2. CAE and particularly f-CHCl 3 caused significant inhibition on tumor growth in mice (40% and 60%, respectively). Uptake of 3 H-thymidine, thus proliferation was reduced in tumor cells from mice treated with CAE (>30%) or f-CHCl 3 (up to 50%) compared to cells from control animals. Data from the trypan blue assay indicating a lower number of tumor cells in treated animals. From the overall, data from this study are in line with the traditional claims for the antitumor effect of Casearia sylvestris . Conclusions This investigation suggests that whether the extracts from Casearia sylvestris are cytotoxic at high concentrations, lower concentrations have antiproliferative effect and could be useful to complement conventional cytotoxic chemotherapy, and should be evaluated further. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Casearia sylvestris is a tree found in tropical America. In Brazil it is known mainly as Guaçatonga. Literature reports suggest that the leaves and other plant parts have been used by indigenous populations from South America in preparations, mainly aqueous or hydroethanolic macerations or decoctions, most times taken orally for the primary treatment of several diseases, including cancer. Aim of the study This article reports the results of an investigation about the antiproliferative effects of Casearia sylvestris on tumor cells in vitro and in vivo . Material and methods Aqueous ethanolic maceration and column chromatography were done to obtain a crude aqueous ethanolic extract (CAE) and a chloroform fraction (f-CHCl 3 ). The human breast cancer cell line MCF-7 was used in culture. In vitro , non-cytotoxic concentrations were determined by MTT assay and the antiproliferative effect was assessed by the colony forming unit assay using non-cytotoxic concentrations. Effects on the cell cycle were observed through flow cytometry using a propidium iodide kit. Casearin C was identified in f-CHCl 3 by chromatography and H 1 nuclear magnetic resonance. The effect on some key proteins of DNA damage (phosphorylation on the histone H2AX) and cell cycle control (p53, p16, cdk2) was evaluated through immunoblot. Antiproliferative effects in vivo were measured in tumor tissue from Ehrlich ascites-bearing mice through the 3 H-thymidine uptake assay and the trypan blue exclusion method. Results In vitro , EC 50 values found at 24 h on MCF-7 cells were 141 µg/mL for CAE and 66 µg/mL for f-CHCl 3 . Inhibition on proliferation was recorded at concentrations as low as 4 µg/mL in the case of the f-CHCl 3 (up to 40%) and up to 50% when CAE was added at 9 µg/mL. The cell cycle arrest was demonstrated by the reduction in terms of number of cells in phases G2/M and S, up to 38.9% and 51.9% when cells were treated with CAE, and 53.9% and 66.2%, respectively, when cells were treated with f-CHCl 3 . The number of cells in G1 was increased when the cells were treated with CAE (21.4%) or f-CHCl 3 (27.8%). Key proteins of cell cycle control were affected. The treatments caused activation of p53, p16 and DNA damage found by the appearance of bands corresponding to γ -H2AX. The treatments caused inhibition of cdk2. CAE and particularly f-CHCl 3 caused significant inhibition on tumor growth in mice (40% and 60%, respectively). Uptake of 3 H-thymidine, thus proliferation was reduced in tumor cells from mice treated with CAE (>30%) or f-CHCl 3 (up to 50%) compared to cells from control animals. Data from the trypan blue assay indicating a lower number of tumor cells in treated animals. From the overall, data from this study are in line with the traditional claims for the antitumor effect of Casearia sylvestris . Conclusions This investigation suggests that whether the extracts from Casearia sylvestris are cytotoxic at high concentrations, lower concentrations have antiproliferative effect and could be useful to complement conventional cytotoxic chemotherapy, and should be evaluated further. [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: Bidens pilosa (L.) (Asteraceae) is a medicinal plant traditionally used in Brazil for treating conditions that can be related to cancer. Therefore the present study was carried out to evaluate the antitumor activity of extracts obtained from the aerial parts of this plant species. Materials and Methods: The crude hydroalcoholic extract (HAE) (water:alcohol, 6:4) and solvent fractions (chloroform=CHCl3 ,ethyl acetate=EtOAc, methanol=MeOH) were assessed for cytotoxicity assay by the brine shrimp and hemolytic, MTT and NRU assays. The antiproliferative potential of the crude extract and fractions was investigated in vivo using the Ehrlich ascites carcinoma (EAC) in isogenic Balb/c mice that were administered intraperitoneally 150 and 300mg/kg body weight per day for nine days beginning 24h after tumor inoculation. Results: In in vitro cytotoxicity using Ehrlich ascites carcinoma cell line assay CHCl3 extract proved to be more toxic than the crude HAE with an IC50 of 97±7.2 and 83±5.2μg/mL to NRU and MTT, respectively. Histomorphological evaluations indicated that the treatment with CHCl3 and HAE extracts significantly reduced (P <0.05) body weight, abdominal circumference, tumor volume, packed cell volume and viable cell count, when compared to EAC control group. Furthermore, nonviable tumor cell count increased significantly (P <0.01) only under treatment with CHCl3 or HAE, and this was accompanied by a marked percentage increase in life span (54.2 and 41.7%, respectively). Biochemical assays revealed that CHCl3 and HAE extracts were also able to decrease serum LDH activity (39.5 and 30.6%) and GSH concentration (94.6 and 50.7%) in ascitic fluid, respectively. Conclusion: The chloroform fraction showed the best and methanolic the worst antitumor activity. [Copyright &y& Elsevier]

Introduction Paraquat (PQ) is an extremely toxic herbicide. The effects of the in vivo exposure to PQ on male fertility and on redox state were investigated in testis and sperm from adult male rats. Methods Adult Wistar male rats received ip injection of 10 mg PQ/Kg body weight or saline during 5 days. After euthanasia, testes and epididymis were dissected and sperm cell viability, motility and teratospermia were evaluated. Moreover, the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) and mieloperoxidase (MPO), as well as the GSH levels and p53 expression were assessed in sperm cells and testis. Results Our data showed that the number, viability and total motility of sperm cells were significantly decreased by PQ exposure. Indeed, we observed an abnormal morphology; identifying teratospermia in PQ exposed animals. We also observed GSH depletion, which was associated with decreased activity of SOD and MPO, while CAT and GST were unaltered by PQ treatment. Moreover, PQ exposure increased p53 expression. Conclusion The PQ-induced male reproductive toxicity is associated with oxidative stress and p53 modulation. [ABSTRACT FROM AUTHOR]