Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used cholesterol-lowering drugs. Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. The objective here was to elucidate the molecular mechanism by which statins induce lymphoma cells death. Statins (atorvastatin, fluvastatin and simvastatin) treatment enhanced the DNA fragmentation and the activation of proapoptotic members such as caspase-3, PARP and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells, which was accompanied by inhibition of cell survival. Both increase in levels of reactive oxygen species (ROS) and activation of p38 MAPK and decrease in mitochondrial membrane potential and activation of Akt and Erk pathways were observed in statin-treated lymphoma cells. Statin-induced cytotoxic effects, DNA fragmentation and changes of activation of caspase-3, Akt, Erk and p38 were blocked by antioxidant (N-acetylcysteine) and metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggests that HMG-CoA reductase inhibitors induce lymphoma cells apoptosis by increasing intracellular ROS generation and p38 activation and suppressing activation of Akt and Erk pathways, through inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP.

Herein, we describe a method for the quantification of Brønsted acid sites located on surfaces and in pores of hierarchical zeolite catalysts. The probe triphenylphosphine (TPP) accesses only pores bigger 0.72 nm. The signal of protonated TPP is baseline separated from other signals and can be directly quantified by 31P MAS NMR spectroscopy. Results are robust and are not affected by the total TPP loading nor by remaining solvent traces. The error of the Brønsted acid site density evaluation is below ±10% for amorphous silica–alumina and below ±5% for probing crystalline materials like MCM-22 or hierarchical zeolites. On amorphous silica–alumina, only 12.5% of all acid sites were accessible by TPP, which binds near tetrahedral and pentahedral aluminum. The 47 ± 2 μmol/g acid sites on the surface and in pore mouths of zeolite MCM-22 represent 12% of the total acidity. On TNU-9, 2% of the total acidity is located on the surface. On commercial zeolite ZSM-5, no surface acidity was found. Desilication of ZSM-5 and TNU-9 zeolites introduced an additional 20 ± 1 and 29 ± 1 μmol/g of Brønsted acid sites, respectively. These additional acid sites are located in introduced mesopores of hierarchical ZSM-5 and TNU-9 zeolites and account for 6–7% of the total sites present. The location in mesopores can cause undesired byproducts in catalysis due to the absence of shape selectivity effects. The techniques described herein will aid the understanding of the acid site density in hierarchical systems and lead to improvements of catalyst synthesis and performance.

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