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Previous work from our laboratory has shown that coupling doxorubicin (Dox) to cell penetrating peptides (Dox-CPPs) is a good strategy to overcome Dox resistance in MDA-MB 231 breast cancer cells. We also reported that, in contrast to unconjugated Dox-induced cell death, the increase in apoptotic response does not involve the mitochondrial apoptotic pathway. In this study, we demonstrate that both Dox and Dox-CPPs can increase the density of the TRAIL receptors DR4 and DR5 at the plasma membrane and moderately sensitize MDA-MB 231 cells to exogeneously added recombinant TRAIL, as has already been shown for other chemotherapeutic drugs. Moreover, we show that Dox-CPPs, used alone, induce the clustering of TRAIL receptors into ceramide-enriched membrane lipid rafts, a property not shared by unconjugated Dox and that this process is due to the generation of ceramide during Dox-CPPs treatment. In addition, MDA-MB 231 cells were found to express TRAIL and we show that the increased apoptotic rate induced by Dox-CPPs is due to the sensitization of MDA-MB 231 cells to endogenous TRAIL. The capacity of Dox-CPPs to sensitize cancer cells to physiologic amounts of TRAIL suggests that, in addition to their efficiency in combination chemotherapy, these compounds might increase the response of tumor cells to cytotoxic lymphocyte-mediated killing via TRAIL.

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Antibacterial antioxidant and cytotoxic activities of petroleum ether, ethyl acetate and methanol extracts of Conyza Canadensis (L.) Cronquist were investigated. Antibacterial activity was evaluated using the agar diffusion and microwell dilution assays against four strains of bacteria. Antioxidant activity was measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and the cytotoxic activity was tested against Hep-2 cells (laryngeal carcinoma cell line) using methylene blue assays. Among tested extracts, the methanolic extract exhibited important antibacterial activity. It also showed good antioxidant activity with 50% inhibition concentration (IC 50 ) of 120 lg/ml. Cytotoxicity of extracts was time depend, increasing with exposure time and concentration. At 72 h of incubation, the ethyl acetate and petroleum ether extracts demonstrated effective cytotoxic activity against Hep-2 cells with IC 50 values of 45 and 50 lg/ml, respectively.