ascorbic-acid and Lymphoma--Follicular

Loss of p53 renders cells more susceptible to acute oxidant stress induced by oxidant-generating agents such as motexafin gadolinium (MGd). We hypothesized that reactive oxygen species (ROS)-generating MGd results in low-level p53 expression, making cells more susceptible to oxidant stress.. Lymphoma cells were incubated with different concentrations of MGd with or without zinc (Zn) and ascorbate, and ROS, apoptosis, proteins, and oxidant genes were measured.. MGd, with ascorbate and Zn, induced apoptosis in lymphoma cells. This was accompanied by reduction of p53 protein but not message, and by reduction of p53 downstream targets p21, glutathione peroxidase 1 (GPx1), and p53 up-regulated modulator of apoptosis (PUMA). p53 protein reduction was reversed by MG132, and nutlin-3.. Our data are consistent with a pathway of cell death that is independent of p53-mediated induction of PUMA; the cellular response to reduce p53 represents a cell survival adjustment to ROS-mediated stress.

Topics: Apoptosis; Ascorbic Acid; Burkitt Lymphoma; Cell Line, Tumor; Gene Expression; Humans; Imidazoles; Leupeptins; Lymphoma, Follicular; Metalloporphyrins; Piperazines; Proto-Oncogene Proteins c-mdm2; Reactive Oxygen Species; Tumor Suppressor Protein p53; Zinc

Although responsive to first-line treatments, follicular lymphoma (FL) remains a fatal disease of increasing worldwide incidence. In efforts to find novel approaches to inhibit proliferation and induce apoptosis in FL cells, we examined the action of naturally occurring compound curcumin in the three recently established FL cell lines.. Cytotoxic effects and determination of apoptotic attributes upon curcumin treatment were analyzed using growth inhibition, [(3)H]-thymidine, fluorescence microscopy, and flow cytometry assays, as well as Western blotting. Chemical inhibitor studies for the assessment of caspase and cathepsin contribution were applied. Expression of 10 members of the bcl-2 family proteins was evaluated by immunoblotting.. Curcumin inhibited proliferation and growth, and induced profound apoptosis associated with a shift in the balance of the bcl-2 family proteins, in all cell lines tested. Strikingly, we observed that curcumin-induced caspase-dependent apoptosis is also associated with lysosomal rupture (LMP). An increase in intracellular ROS generation appeared critical for curcumin-evoked LMP, loss of Deltapsi(m,) caspase activation, and cell death, as well as ascorbic acid-mediated enhancement of curcumin's action.. We have demonstrated for the first time that curcumin is an efficient inducer of apoptosis in FL cell lines, meriting its further evaluation in vivo.

Topics: Antineoplastic Agents; Apoptosis; Ascorbic Acid; Caspases; Cell Line, Tumor; Cell Proliferation; Curcumin; Drug Evaluation, Preclinical; Drug Synergism; Enzyme Activation; Humans; Lymphoma, Follicular; Lysosomes; Membrane Potentials; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Vitamins