Catalase

Research reports on lymphoma from S. Sieber and colleagues provide new insights

"In the present investigation, we analyzed, whether a combination of rituximab and artesunate may act in a complementary manner and eventually synergize in tumor cell killing. Artesunate is an anti-malarial drug, which also exerts profound activity towards cancer cells. While rituximab alone was minimally cytotoxic, rituximab increased cytotoxicity to artesunate in Ramos cells. Artesunate induced apoptosis, induced Fas/CD95 expression and the formation of reactive oxygen species (ROS) and resulted in a breakdown of mitochondrial membrane potential. This argues for the involvement of both receptor-driven extrinsic and mitochondrial intrinsic routes of apoptosis. Rituximab increased Fas/CD95 expression and ROS formation and decreased mitochondrial membrane potential ultimately leading to increased apoptosis induced by artesunate. The transcription factors YY1 and Sp1 are upstream regulators of apoptosis by controlling the expression of apoptosis-regulating genes. YY1 and Sp1 were down-regulated and Fas/CD95 was up-regulated by rituximab and artesunate indicating that artesunate activated the Fas/CD95 pathway and that rituximab increased the Susceptibility of tumor cells to artesunate-induced apoptosis. Furthermore, rituximab affected the expression of antioxidant genes. The antibody decreased artesunate-induced up-regulation of catalase expression and increased artesunate-induced down-regulation of glutathione S-transferase-in expression. Manganese-dependent Superoxide dismutase expression was not changed by artesunate. Antioxidant proteins may help to detoxify artesunate-induced ROS. Rituximab reversed the artesunate-induced expression changes of antioxidant genes and, hence, reduced the detoxification capacity of Ramos cells," wrote S. Sieber and colleagues.

The researchers concluded: "The effects of rituximab oil antioxidant genes represent a novel mechanism of rituximab. for chemosensitization.."

Sieber and colleagues published their study in International Journal of Oncology (Combination treatment of malignant B cells using the anti-CD20 antibody rituximab and the anti-malarial artesunate. International Journal of Oncology, 2009;35(1):149-158).

For additional information, contact T. Efferth, German Cancer Research Center, Pharmaceutical Biology C015, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

The publisher's contact information for the International Journal of Oncology is: Professor D a Spandidos, 1, S Merkouri St., Editorial Office, Athens 116 35, Greece.

Keywords: Germany, Heidelberg, Anticancer Therapy, Apoptosis, B-Cell Lymphoma, Biotechnology, Cancer, Chemotherapy, Drug Development, Drug Resistance, Drug Therapy, Hematology, Malaria, Medical Device, Monoclonal Antibodies, Monoclonal Antibody, Oncology, Pharmaceuticals, Therapy, Treatment.

This article was prepared by Anti-Infectives Week editors from staff and other reports. Copyright 2009, Anti-Infectives Week via NewsRx.com.