Antioxidant, antiproliferative and healing properties of araticum (Annona crassiflora Mart.) peel and seed.

Araticum (Annona crassiflora Mart.) is a native fruit from Brazilian Cerrado widely used by folk medicine. Nevertheless, the biological effects of its seeds and peel have not been extensively evaluated. We evaluate herein the antioxidant, antiproliferative and healing potential of araticum peel and seeds extracts. HPLC-ESI-MS/MS analysis showed flavonoids, namely epicatechin and quercetin, as the main compounds in peel and seeds extracts, respectively. These extracts showed high content of phenolic compounds (7254.46 and 97.74 µg/g extract) and, as consequence, high antioxidant capacity. Interesting, the seeds extract was more effective than peel extract against all tested cancer cells, especially on NCI-ADR/RES (multidrug resistant ovary adenocarcinoma) cell line. In the cell migration assay by using HaCaT (keratinocyte), the seeds extract induced migration, while the peel extract showed an inhibitory effect. In this way, phenolic content could be related to antioxidant capacity, but it was not related to antiproliferative and healing effect. The araticum seeds extract showed an interesting response to in vitro biological assay although of its low content of phenolic compounds. Unidentified compounds, such as alkaloids and annonaceous acetogenins could be related to it. Araticum has potential to be used as therapeutic plant especially as antiproliferative and healing drug.

Antiangiogenic therapy with Nintedanib affects hypoxia, angiogenesis and apoptosis in the ventral prostate of TRAMP animals.

The antiangiogenic therapy for prostate cancer with Nintedanib, a potent inhibitor of important growth factor receptors, has been proven to delay tumor progression and arrest tumor growth; thus, the aim herein is to evaluate Nintedanib effects on tumor cells, besides angiogenesis and apoptosis processes, metalloproteinases and hypoxia factor in an animal model. Nintedanib promoted growth inhibition and cell death in a dose-dependent manner, showing no tumor selectivity. Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) were treated with Nintedanib (10 mg/kg/day) in different stages of tumor development and the ventral prostate was examined for protein levels by means of immunohistochemistry and Western blotting and apoptosis evaluation. In vitro antiproliferative activity of Nintedanib was also assessed in nine human tumor cell lines. Early Nintedanib treatment has shown decreased levels of FGF-2, VEGFR-1, MMP-9 and HIF-1α and a significantly increased apoptosis of epithelial cells. Furthermore, late Nintedanib treatment decreased FGF-2, VEGFR-1 and FGFR-3 levels. Importantly, even after treatment discontinuation, treated animals displayed a significant decrease in VEGFR-1 as well as MMP-9. Although Nintedanib treatment in late stages of tumor growth has shown some good results, it is noteworthy that the drug presents the best tissue response when administered in the early stages of disease development. Nintedanib treatment has shown to be a promising approach for prostate cancer therapy, especially in the early stages of the disease, interfering in different carcinogenesis progression pathways.

Antiproliferative Effect of Urera baccifera Leaves Against Ovarian Carcinoma Cell Line (OVCAR-3)

Abstract Natural products, especially phytochemicals, have been extensively studies and have exhibited important antiproliferative effects. The American native species Urera baccifera (L.) Gaudich. ex Wedd. (Urticaceae) is widely distributed in Brazil, where it is known as urtiga-vermelha or urtigão. The leaves are popularly used as anti-inflammatory, antirheumatic and in the treatment of gastric disorders. However, the antiproliferative potential of this plant against human tumor cells remain to be elucidated. In this study, we evaluated the antiproliferative effects of U. baccifera leaves extracts and fractions against a panel of human tumor cell lines in vitro besides a chemical evaluation of the most active sample by mass spectrometry (ESI-IT-MSn). The hydroalcoholic extract was inactive while dichloromethane extract showed moderate cytostatic activity against ovarian carcinoma cell line (OVCAR-3, GI50 = 1.5 μg/mL). More, the ethyl acetate and n-butanol fractions did not show important activity against tumour cell while the dichloromethane and hexane fractions showed moderate cytostatic activity against ovarian tumor cell line (OVCAR-3, GI50 = 12.7 and 9.4 μg/mL, respectively). Finally, the chemical profile evaluated by mass spectrometry (ESI-IT-MSn) allowed the detection of flavonoids in the HEU and hydroxylated fatty acid in DEU that can explain partially the biological effects observed. This is the first report of the antiproliferative effects of U. baccifera, and DEU has shown potential as a promising source of bioactive compounds.