6-Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species

Combination therapies, using medicinal herbs, are broadly recommended to attenuate the chemotherapy adverse effects. Based on our previous findings considering the anti-leukaemic effects of ginger extract on acute lymphoblastic leukaemia (ALL) cells, the present study was aimed to investigate the anti-cancer role of this pharmaceutical plant on ALL mice models. Moreover, we worked towards identifying the most anti-leukaemic derivative of ginger and the mechanism through which it may exert its cytotoxic impact. In vivo experiments were performed using five groups of six C57BL/6 nude mice, and the anti-leukaemic activity of ginger extract alone or in combination with methotrexate (MTX) was examined. Results showed increased survival rate and reduced damages in mice brain and liver tissues. Subsequently, MTT assay demonstrated synergistic growth inhibitory effect of 6-shogaol (6Sh) and MTX on ALL cell lines and patients primary cells. Eventually, the molecular anti-neoplastic mechanism of 6Sh was evaluated using Bioinformatics. Flow cytometry illustrated 6Sh-mediated apoptosis in Nalm-6 cells confirmed by Western blotting and RT-PCR assays. Further analyses exhibited the generation of reactive oxygen species (ROS) through 6Sh. The current study revealed the in vivo novel anti-leukaemic role of ginger extract, promoted by MTX. Moreover, 6-shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation.     

Detection of P-glycoprotein on endothelial and endocrine cells of the human pancreatic islets by C 494 monoclonal antibody

Summary P-glycoprotein, an integral membrane protein acting as an energy-dependent efflux pump, has been detected immunocytochemically in the human pancreatic islets using C 494 monoclonal antibody. Intense P-glycoprotein immunoreactivity was found in both endothelial cells of islet blood capillaries and in endocrine cells. Strong expression of P-glycoprotein has been found in the capillary blood vessels at blood-tissue barrier sites and in numerous kinds of cells with secretory/excretory function. Therefore the present findings suggest that P-glycoprotein may play a role in controlling the composition of the extracellular fluids and the intracellular milieu of endocrine islet cells and possibly in regulating their secretory activity.     

Intermediate cell tumour of the pancreas in rat

A malignant tumour of the rat pancreas with features of both acinar and endocrine cells is presented. This consisted of a continuous cytoplasmic mass with numerous dispersed nuclei and branches protruding from its borders invading the surrounding exocrine tissue. The most prominent characteristic of the tumour was the co-existence of zymogen and endocrine secretory granules and cytoplasmic organelles typical of both acinar and islet cells. Some hypotheses are put forward concerning the origin of the tumour and its vasculature.     

Isopongaglabol and 6-methoxyisopongaglabol,two new hydroxyfuranoflavones from Pongamia glabra

Isopongaglabol and 6-methoxyisopongaglabol, two new hydroxyfuranoflavones, together with two furanoflavones 5-methoxyfurano(8,7-4″,5″)flavone and 5-methoxy-3′,4′-methylenedioxyfurano(8,7-4″,5″)flavone, two simple flavones, desmethoxykanugin and fisetin tetramethyl ether, a chromenoflavanone, ovalichromene B, two triterpenes, cycloart-23-ene-3β,25-diol and friedelin, and β-sitosterol-β-d-glucoside were isolated from the petrol and CHCl₃ extracts of the flowers of Pongamia glabra. The structures of isopongaglabol and 6-methoxyisopongaglabol have been established as 4′-hydroxyfurano(8,7-4″,5″)flavone and 4′-hydroxy-6-methoxyfurano(8,7-4″,5″)flavone, respectively, on the basis of the spectral evidence and they have been confirmed by synthesis.