Search results for "Anticancer"
showing 10 items of 171 documents
Folate-targeted supramolecular vesicular aggregates as a new frontier for effective anticancer treatment in in vivo model.
2012
Abstract Supramolecular vesicular aggregates (SVAs), made up by self-assembling liposomes and polyasparthydrazide co-polymers conjugated to folic acid molecules were extensively investigated in this manuscript as potential active targeting formulation for anticancer drug delivery. Folate-targeted systems (FT-SVAs) were used to treat breast cancer and to further proof the potential in vivo administration of these systems for the therapeutic treatment for several aggressive solid tumors. The physicochemical and technological parameters of FT-SVAs are suitable for their potential in vivo administration. The chemotherapeutic activity of GEM-loaded FT-SVAs was increased during in vivo experiment…
Stilbene-based anticancer agents: Resveratrol analogues active toward HL60 leukemic cells wit a non-specific phase mechanism
2006
Several stilbenes, related to known resveratrol, have been synthesized and tested for their anticancer effect on HL60 leukemia cell line, taking particular care of the cell cycle analysis. The most potent compound was the known (Z)-3,4',5-trimethoxystilbene (6b) which was active as apoptotic agent at 0.24 microM. Differently from other stilbenes (including resveratrol) that induced a prevalent recruitment of cells in S phase of cell cycle, we found a peculiar behavior of 6b that caused a decrease of cells in all phases of cell cycle (G0-G1, S, and G2-M) and a proportional increase of apoptotic cells. The potent pro-apoptotic activity shown by compound 6b and its effects on cell cycle make t…
Bax-derived membrane-active peptides act as potent and direct inducers of apoptosis in cancer cells.
2011
SUMMARYAlthough many cancer cells are primed for apoptosis, they usually develop resistance to cell death at multiple levels. Permeabilization of the outer mitochondrial membrane, which is mediated by proapoptotic Bcl-2 family members like Bax, is considered as a point-of-no-return for initiating apoptotic cell death. This crucial role has placed Bcl-2 family proteins as recurrent targets for anticancer drug development. Here, we propose and demonstrate a new concept based on using minimal active version of Bax to induce cell death independently of endogenous Bcl-2 proteins. We show that membrane-active segments of Bax can directly induce the release of mitochondria-residing apoptogenic fac…
Polyaspartamide-Doxorubicin Conjugate as Potential Prodrug for Anticancer Therapy
2015
Purpose To synthesize a new polymeric prodrug based on ?,?- poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide copolymer bearing amine groups in the side chain (PHEA-EDA), covalently linked to the anticancer drug doxorubicin and to test its potential application in anticancer therapy. Methods The drug was previously derivatized with a biocompatible and hydrophilic linker, leading to a doxorubicin derivative highly reactive with amino groups of PHEA-EDA. The PHEAEDA- DOXO prodrug was characterized in terms of chemical stability. The pharmacokinetics, biodistribution and cytotoxicity of the product was investigated in vitro and in vivo on human breast cancer MCF-7 and T47D cell lin…
Encapsulation capacity and natural payload delivery of an anticancer drug from boron nitride nanotube.
2016
The behavior of confined anticancer carboplatin (CPT) molecules in a single (10, 10) boron nitride nanotube (BNNT) was studied by means of molecular dynamics simulations. Our study revealed a very large storage capacity of BNNT. Analysis of the energy profiles depending on the number of confined molecules, and on their spatial organization allowed us to quantify the ability of BNNT to vectorize CPT. Indeed, BNNT despite its small radius presented a large inner volume that favored stable encapsulation of multiple active anticancer molecules. Moreover, in our molecular dynamics simulations, the empty BNNT and the BNNT filled with CPT diffused spontaneously to the cell membrane and were able t…
GSK3β as a novel promising target to overcome chemoresistance in pancreatic cancer
2021
Pancreatic cancer is an aggressive malignancy with increasing incidence and poor prognosis due to its late diagnosis and intrinsic chemoresistance. Most pancreatic cancer patients present with locally advanced or metastatic disease characterized by inherent resistance to chemotherapy. These features pose a series of therapeutic challenges and new targets are urgently needed. Glycogen synthase kinase 3 beta (GSK3β) is a conserved serine/threonine kinase, which regulates key cellular processes including cell proliferation, DNA repair, cell cycle progression, signaling and metabolic pathways. GSK3β is implicated in non-malignant and malignant diseases including inflammation, neurodegenerative …
Apoptotic effects of thiazolobenzimidazole derivatives on sensitive and multidrug resistant leukaemic cells
2001
We investigated the cytotoxic activity of eight thiazolobenzimidazole derivatives on sensitive HL60 and multidrug-resistant (MDR) (HL60R) leukaemia cell lines. The antitumour effects of these compounds were compared with those of RS-TBZ, a thiazolobenzimidazole derivative, previously described in our reports, that was able to induce apoptosis more markedly in MDR cells than in the parental sensitive cell lines. Only two compounds in this study proved to have interesting effects: (a) the S-enantiomer of TBZ, that was able to induce apoptosis in MDR cells in a slightly more selective manner than TBZ (racemic form); and (b) TBZ-4-OCH3 (TBZ-4-OCH3), that showed cytotoxic and apoptotic effects o…
Nanofitins targeting heat shock protein 110: an innovative immunotherapeutic modality in cancer.
2021
The presence of an inactivating heat shock protein 110 (HSP110) mutation in colorectal cancers has been correlated with an excellent prognosis and with the ability of HSP110 to favor the formation of tolerogenic (M2-like) macrophages. These clinical and experimental results suggest a potentially powerful new strategy against colorectal cancer: the inhibition of HSP110. In this work, as an alternative to neutralizing antibodies, Nanofitins (scaffold ~7 kDa proteins) targeting HSP110 were isolated from the screening of a synthetic Nanofitin library, and their capacity to bind (immunoprecipitation, biolayer interferometry) and to inhibit HSP110 was analyzed in vitro and in vivo. Three Nanofiti…
Beyond cholesterol reduction, the pleiotropic effects of statins: is their use in cancer prevention hype or hope?
2013
ISSN 1758-4299 10.2217/CLP.13.29 © 2013 Future Medicine Ltd Clin. Lipidol. (2013) 8(3), 273–277 Pleiotropic effects of statins Millions of patients worldwide are currently tak ing prescribed statins. Clinical trials have dem onstrated that statins reduce the risk of cardio vascular disease [1]. Statins are well known to reduce cholesterol levels through the inhibition of 3hydroxymethylglutaryl CoA reductase [2]. However, great interest has recently been paid to the mechanisms beyond cholesterol reduc tion (pleiotropic effects) by which statins exert their action. Indeed, statins are associated with plaque stabilization and improvement of endo thelial function, as well as antiinflamm…
Molecular Approaches to Target Heat Shock Proteins for Cancer Treatment
2015
HSP90 was the first molecular target to inhibit the interaction of this heat shock protein (HSP) with client proteins in cancer cells and tissues. The HSP90 inhibition was attempted to liberate from this chaperone the oncogenic fusion proteins, mutated and activated serine/threonine protein kinases, tyrosine kinases, as well as transcription factors with oncogenic activity, in this manner, the free proteins could be recognized by the proteasome system to be degraded. We should remember here that many HSP family members are overexpressed in different kinds of cancer tissues, these molecules act as chaperones of tumorigenesis. In cancer patients, the first generation of HSP90 inhibitors showe…