Olive Phenolics as c-Met Inhibitors: (-)-Oleocanthal Attenuates Cell Proliferation,Invasiveness, and Tumor Growth in Breast Cancer Models

Dysregulation of the Hepatocyte growth factor (HGF)/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT), angiogenesis, invasion, and metastasis. (-)-Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (-)-oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (-)-oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (-)-oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (-)-oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (-)-oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (-)-oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.     

The endangered maned sloth Bradypus torquatus of the Brazilian Atlantic forest: a review and update of geographical distribution and habitat preferences

• 1 The endemic maned sloth Bradypus torquatus is globally threatened due to deforestation, habitat fragmentation and isolation of populations. Despite increased interest in the species in recent years, information on its geographic distribution is limited and is derived mainly from a few museum species and from a survey based mostly on interviews carried out more than 20 years ago. Information on its habitat and altitudinal preferences is lacking. We therefore compile, update and review all occurrence records of this species using geographical information system (GIS) tools and produce a distribution map for the species.
• 2 Our compilation totalled 188 occurrence records, of which 130 (69%) were considered confirmed (museum specimens or individuals captured or seen in the field), most of which (62%) were restricted to the states of Bahia and central‐south Espírito Santo (29%). The species occurs predominantly in ombrophilous forest (80%), from sea level to 1290m, but mainly (79%) below 200m altitude.
• 3 We used GIS techniques and the alpha shape algorithm to calculate the extent of occurrence of the species and compared the resulting map with distribution maps available in the literature. We found a great deal of variation in distribution area shape and an almost two‐fold variation in distribution area size among sources.
• 4 We confirmed the existence of a main distribution gap between southern Bahia and northern Espírito Santo and discovered a second smaller gap between southern Espírito Santo and northern Rio de Janeiro.
• 5 We also confirmed that B. torquatus is sympatric with the common three‐toed sloth Bradypus variegatus in a large part of the Atlantic forest and that the two species are syntopic in at least 11 locations.