RESUMO
Cancerous tissue transformation developing usually over years or even decades of life is a highly complex process involving strong stressors damaging DNA, chronic inflammation, comprehensive interaction between relevant molecular pathways, and cellular cross-talk within the neighboring tissues. Only the minor part of all cancer cases are caused by inborn predisposition; the absolute majority carry a sporadic character based on modifiable risk factors which play a central role in cancer prevention. Amongst most promising candidates for dietary supplements are bioactive phytochemicals demonstrating strong anticancer effects. Abundant evidence has been collected for beneficial effects of flavonoids, carotenoids, phenolic acids, and organosulfur compounds affecting a number of cancer-related pathways. Phytochemicals may positively affect processes of cell signaling, cell cycle regulation, oxidative stress response, and inflammation. They can modulate non-coding RNAs, upregulate tumor suppressive miRNAs, and downregulate oncogenic miRNAs that synergically inhibits cancer cell growth and cancer stem cell self-renewal. Potential clinical utility of the phytochemicals is discussed providing examples for chemoprevention against and therapy for human breast cancer. Expert recommendations are provided in the context of preventive medicine.
Assuntos
Anticarcinógenos/farmacologia , Neoplasias da Mama/prevenção & controle , Compostos Fitoquímicos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carotenoides/farmacologia , Proliferação de Células/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Metástase Neoplásica/prevenção & controle , Células-Tronco Neoplásicas/efeitos dos fármacos , Neovascularização Patológica/prevenção & controle , Fenóis/farmacologia , RNA não Traduzido/efeitos dos fármacos , Compostos de Enxofre/farmacologiaRESUMO
Submucosal injection is often required step during endoscopic mucosal resection (EMR). In clinical practice we have observed that the EMR injection solution containing hetastarch (HES) lead to selective increase of the neoplasms volume, facilitating their resection. The aim of this study was to explore the possible mechanisms of such behaviour, which was not reported elsewhere. The HCT116 cell line of human colon cancer was exposed to the same EMR solution in vitro. The significant volume increase of HCT116 cells was observed, but only for starving cell culture, suggesting that the starving is essential for the neoplasms-specific volume change. We suggest, that for the iso-oncotic composition of the EMR submucosa injection solution the HES component is crucial, as it can be subject of the starch hydrolysis followed by facilitated transport of resulting monosaccharides from the submucosa into the neoplastic tissue.
Assuntos
Adenoma , Ressecção Endoscópica de Mucosa , Humanos , Derivados de Hidroxietil Amido/farmacologia , Mucosa Intestinal/cirurgia , Adenoma/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Monossacarídeos , Resultado do TratamentoRESUMO
Multifunctional nanoparticulate systems, especially those used in medicine, are currently of great interest. In this work, the in-vitro anticancer activity of As4S4/Fe3O4 composites dispersed in a water solution of Poloxamer 407 on breast MCF-7 and tongue SCC-25 cancer cells was verified. An increase in apoptotic cells as a consequence of higher caspase activities, a decrease in mitochondrial membrane potential and an accumulation of cells in the G2/M and subG0/G1 phases were detected after treatment with the As4S4/Fe3O4 nanosuspensions. The sterically stabilized nanosuspensions were characterized in relation to their particle size distribution, zeta potential and long-term stability properties. The interaction between the solid and liquid phases of the nanosuspensions was also studied using Fourier transform infrared spectroscopy.
Assuntos
Antineoplásicos/farmacologia , Arsenicais/farmacologia , Compostos Férricos/farmacologia , Nanopartículas/química , Sulfetos/farmacologia , Suspensões/química , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Fenômenos Magnéticos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanocompostos/química , Nanocompostos/ultraestrutura , Tamanho da Partícula , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , TemperaturaRESUMO
Lichens are a known source of approximately 800 unique secondary metabolites, many of which play important ecological roles, including regulating the equilibrium between symbionts. However, only a few of these compounds have been assessed for their effectiveness against various in vitro cancer models. Moreover, the mechanisms of biological activity of lichen secondary metabolites on living cells (including cancer cells) are still almost entirely unknown. In the present study, we investigated the mechanisms of cytotoxicity of four lichen secondary metabolites (parietin, atranorin, usnic acid and gyrophoric acid) on A2780 and HT-29 cancer cell lines. We found that usnic acid and atranorin were more effective anti-cancer compounds when compared to parietin and gyrophoric acid. Usnic acid and atranorin were capable of inducing a massive loss in the mitochondrial membrane potential, along with caspase-3 activation (only in HT-29 cells) and phosphatidylserine externalization in both tested cell lines. Induction of both ROS and especially RNS may be responsible, at least in part, for the cytotoxic effects of the tested compounds. Based on the detection of protein expression (PARP, p53, Bcl-2/Bcl-xL, Bax, p38, pp38) we found that usnic acid and atranorin are activators of programmed cell death in A2780 and HT-29, probably through the mitochondrial pathway.