Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer

Background: In this study we investigated the in vitro and in vivo anticancer effect of carnosol, a naturally occurring polyphenol, in triple negative breast cancer.Results: We found that carnosol significantly inhibited the viability and colony growth induced G2 arrest in the triple negative MDA-MB-231. Blockade of the cell cycle was associated with increased p21/WAF1 expression and downregulation of p27. Interestingly, carnosol was found to induce beclin1-independent autophagy and apoptosis in MDA-MB-231 cells. The coexistence of both events, autophagy and apoptosis, was confirmed by electron micrography. Induction of autophagy was found to be an early event, detected within 3 h post-treatment, which subsequently led to apoptosis. Carnosol treatment also caused a dose-dependent increase in the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Moreover, we show that carnosol induced DNA damage, reduced the mitochondrial potential and triggered the activation of the intrinsic and extrinsic apoptotic pathway. Furthermore, we found that carnosol induced a dose-dependent generation of reactive oxygen species (ROS) and inhibition of ROS by tiron, a ROS scavenger, blocked the induction of autophagy and apoptosis and attenuated DNA damage. To our knowledge, this is the first report to identify the induction of autophagy by carnosol.Conclusion: In conclusion our findings provide strong evidence that carnosol may be an alternative therapeutic candidate against the aggressive form of breast cancer and hence deserves more exploration.Scopu

Mosquito biodiversity and mosquito-borne viruses in the United Arab Emirates

Abstract Background In the last 50 years, the United Arab Emirates (UAE) has experienced rapid population growth and urbanization. Urbanization is known to influence biodiversity, and there appears to be a link between the emergence of arboviruses and urban growth. Very little is known about the UAE mosquito species richness and dominant vectors. We performed a mosquito survey comparing peri-urban sites in Dubai and Al Ain to a protected, natural site in Fujairah emirate. We measured mosquito biodiversity and species composition, and screened mosquito pools for common arboviruses to measure arbovirus activity in the region. Results We report ten species of mosquitoes from the UAE, with highest species diversity in the natural site, a protected wadi near the eastern coast. The predominant mosquito was Culex perexiguus, and was associated with peri-urban habitats. The site with lowest mosquito species diversity but relatively high species richness was the peri-urban site of Al Ain Zoo, where we identified Bagaza virus and Barkedji virus, two flaviviruses, in pools of Cx. perexiguus. Conclusions Decreased mosquito biodiversity was associated with increased levels of urbanization. The predominance of two species at peri-urban sites was related to the availability of their larval habitats. Arboviruses were associated with the presence of a single predominant mosquito species, Cx. perexiguus