RESUMO
Flotillin-1 and flotillin-2 are highly conserved proteins that localize into cholesterol-rich microdomains in cellular membranes. Flotillins are closely related to the occurrence and development of various types of human cancers. Flotillin-1 is highly expressed in breast cancer, and the high expression level of flotillin-1 is significantly correlated with poorer patient survival. Here we studied the relationship between the formation of lipid rafts and the expression of flotillins and lipids in human breast cancer cells. We used the polyphenol compound resveratrol to alter the structure and function of the plasma membrane. Our data revealed an increase in fatty acids in MCF-7 and MDA-MB-231 cells upon resveratrol treatment. Interestingly, we also found an increase in the expression of both flotillin-1 and flotillin-2 in breast tumor cells after treatment. Resveratrol also induced changes in the pattern of flotillin distribution among detergent-resistant lipid rafts fractions in both cell lines and induced the nuclear translocation of flotillin-2. Since resveratrol has been pointed out as a putative cancer therapy agent, our results could have an impact on the understanding of the effects of resveratrol in tumor cells.
Assuntos
Antioxidantes/farmacologia , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácidos Graxos/metabolismo , Proteínas de Membrana/metabolismo , Resveratrol/farmacologia , Neoplasias da Mama/metabolismo , Membrana Celular/metabolismo , Humanos , Células MCF-7 , Microdomínios da Membrana/efeitos dos fármacos , Microdomínios da Membrana/metabolismoRESUMO
BACKGROUND: Stilbene-based compounds show antitumoral, antioxidant, antihistaminic, anti-inflammatory and antimicrobial activities. Here, we evaluated the effect of the trans-resveratrol analogs, pterostilbene, piceatannol, polydatin and oxyresveratrol, against Leishmania amazonensis. METHODOLOGY/PRINCIPAL FINDINGS: Our results demonstrated a low murine macrophage cytotoxicity of all four analogs. Moreover, pterostilbene, piceatannol, polydatin and oxyresveratrol showed an anti-L. amazonensis activity with IC50 values of 18 µM, 65 µM, 95 µM and 65 µM for promastigotes, respectively. For intracellular amastigotes, the IC50 values of the analogs were 33.2 µM, 45 µM, 29 µM and 30.5 µM, respectively. Among the analogs assayed only piceatannol altered the cell cycle of the parasite, increasing 5-fold the cells in the Sub-G0 phase and decreasing 1.7-fold the cells in the G0-G1 phase. Piceatannol also changed the parasite mitochondrial membrane potential (ΔΨm) and increased the number of annexin-V positive promastigotes, which suggests incidental death. CONCLUSION/SIGNIFICANCE: Among the analogs tested, piceatannol, which is a metabolite of resveratrol, was the more promising candidate for future studies regarding treatment of leishmaniasis.