Acetonic Extract of Buxus sempervirens Induces Cell Cycle Arrest, Apoptosis and Autophagy in Breast Cancer Cells

Plants are an invaluable source of potential new anti-cancer drugs. Here, we investigated the cytotoxic activity of the acetonic extract of Buxus sempervirens on five breast cancer cell lines, MCF7, MCF10CA1a and T47D, three aggressive triple positive breast cancer cell lines, and BT-20 and MDA-MB-435, which are triple negative breast cancer cell lines. As a control, MCF10A, a spontaneously immortalized but non-tumoral cell line has been used. The acetonic extract of Buxus sempervirens showed cytotoxic activity towards all the five studied breast cancer cell lines with an IC50 ranging from 7.74 µg/ml to 12.5 µg/ml. Most importantly, the plant extract was less toxic towards MCF10A with an IC50 of 19.24 µg/ml. Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a and BT-20 cell lines, concomitant to cyclin D1 downregulation. Application of MCF7 and MCF10CA1a respective IC50 did not show such effects on the control cell line MCF10A. Propidium iodide/Annexin V double staining revealed a pre-apoptotic cell population with extract-treated MCF10CA1a, T47D and BT-20 cells. Transmission electron microscopy analyses indicated the occurrence of autophagy in MCF7 and MCF10CA1a cell lines. Immunofluorescence and Western blot assays confirmed the processing of microtubule-associated protein LC3 in the treated cancer cells. Moreover, we have demonstrated the upregulation of Beclin-1 in these cell lines and downregulation of Survivin and p21. Also, Caspase-3 detection in treated BT-20 and T47D confirmed the occurrence of apoptosis in these cells. Our findings indicate that Buxus sempervirens extract exhibit promising anti-cancer activity by triggering both autophagic cell death and apoptosis, suggesting that this plant may contain potential anti-cancer agents for single or combinatory cancer therapy against breast cancer

A New Tool to Model Parallel Systems and Protocols

We present a new performance evaluation tool based on the analysis of large Markov chains and Stochastic Automata Networks. Using some graph theoretical arguments, we show how to systematically perform state reduction. The graph properties can be checked easily because we take advantage of the tensorial construction of the Markov chain from the Stochastic Automata Network. 1 Introduction We present a new modeling tool based on Stochastic Automata Networks (SAN). Stochastic Automata Networks have been introduced as an efficient method to represent complex systems with interacting components such as parallel systems or distributed systems [Plateau et al. 1988]. This new method automatically provides an analytic derivation of the generator matrix of the Markov chain using tensor algebra. The SAN seem to be more efficient than Queueing Networks or Stochastic Petri Nets to model systems with a large number of states and complex synchronizations. Queueing Networks give a very compact repres..

Multiple Class G-Networks with Jumps back to Zero

We consider multiple class G-networks of processor sharing queues with negative customers which destroy all the customers in a queue. We prove that these networks have a product form solution for steady-state distribution. These networks may have some applications in reliability or performability as the negative customers may clearly model breakdown of computer or communication systems. We also show that under simple assumptions these networks always have a stationary distribution. Finally, we present some asymptotic results on the average number of customers and the average sojourn time when the arrival rate goes to infinity

Performance Modelling of Hierarchical Cellular Networks using PEPA

. We present a performance evaluation study of hierarchical cellular networks using PEPA. These networks constitute a new application area for this process algebra formalism. We show that this formalism can easily be used to model such systems. We also show that the strong equivalence aggregation technique behind PEPA allows a significant reduction of the state space of the underlying Markov process. Using the resulting model, we derive performance criteria such as new call blocking and dropping handover probabilities. 1 Introduction Hierarchical cellular networks [2] have been proposed for future Personal Communications Systems [4] in the frame of third generation of wireless networks (UMTS). In these networks, a service area is called a cell and is defined as the area where the received signal power from a base station is stronger than the signals from all other base stations. Depending on the expected traffic density and on their sizes, cells are of two types: large cells or macroc..