Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells

Malignant melanoma is the leading cause of death from skin cancer. Drug toxicity and resistance represent a serious challange for melanoma treatments. Evidence demonstrates that natural compounds may play a crucial role in cancer prevention, growth and progression. Vitamin E tocotrienols (TT) were shown to possess antitumor activity. Here, we analyzed the effects of \u3b4-TT on melanoma cell growth and the involvement of the endoplasmic reticulum (ER) stress in this activity. The experiments were performed on human melanoma cell lines, BLM and A375. \u3b4-TT exerted a significant proapoptotic effect on both cell lines, involving the intrinsic apoptosis pathway; importantly, this compound did not affect the viability of normal human melanocytes. In melanoma cells, \u3b4-TT exerted its antitumor effect through activation of the PERK/p-eIF2\u3b1/ATF4/CHOP, IRE1\u3b1 and caspase-4 ER stress-related branches. Salubrinal, an inhibitor of the ER stress, counteracted the cytotoxic activity of \u3b4-TT. In vivo experiments performed in nude mice bearing A375 xenografts evidenced that \u3b4-TT reduces tumor volume and tumor mass; importantly, tumor progression was significantly delayed by \u3b4-TT treatment. In conclusion, \u3b4-TT exerts a proapoptotic activity on melanoma cells, through activation of the ER stress-related pathways. \u3b4-TT might represent an effective option for novel chemopreventive/therapeutic strategies for melanoma

Systemic Complement Activation in Age-Related Macular Degeneration

Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001), were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes

Bollettino del R. Comitato geologico d\u27Italia.

v.48 (1920-1921

Bollettino del R. Comitato geologico d\u27Italia.

v.49 (1922-1923

Bollettino del R. Comitato geologico d\u27Italia.

v.46 (1916-1918

Examen de Física C del 2014-1S de la 1° evaluación

v.5(1874

Commission des Communautes Europeennes: Groupe du Porte-Parole. Rendez-vous de midi du lundi 8 septembre 1980 (J. Carroll) = Commission of European Communities: Spokesman Group. Appointment on the afternoon of Monday, 8 September 1980 (J. Carroll). Spokesman Service Note to National Offices Bio No. (80) 341, 8 September 1980

v.42(1911-1912

Bollettino del R. Comitato geologico d\u27Italia.

v.15(1884

Bollettino del R. Comitato geologico d\u27Italia.

v.37(1906