Combinatorial Effect of Non-Steroidal Anti-inflammatory Drugs and NF-κB Inhibitors in Ovarian Cancer Therapy

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer

Dealumination of mordenite zeolite and its catalytic performance evaluation in m-xylene isomerization reaction

Mordenite zeolite with Si/Al = 18 was successfully synthesized by the hydrothermal method. This zeolite was modified by partially dealuminated in HNO3 at 70 °C. Our analysis showed that the surface area of modified mordenite was increased more than that of the mordenite zeolite. Acid leaching removes impurities and aluminium from the zeolite network, improving Si/Al ratio of the framework and increasing the external surface area of the zeolite.The catalytic performances of these synthesized catalysts were investigated for meta-xylene isomerization reaction in a fixed bed reactor. The performances were then benchmarked with the performance of SAPO-11, a commercially available catalyst.The results showed that p-xylene/o-xylene ratio over the catalysts was found to be in the order: dealuminated mordenite > mordenite > SAPO-11, however dealuminated mordenite and SAPO-11 gave higher m-xylene conversion than that of the mordenite