MGN-3 Potentiates Death Receptor-induced Apoptosis

# C313 MGN-3 potentiates death receptor-induced apoptosis in cancer cells.

Mamdooh Ghoneum and Sastry Gollapudi,

Drew University of Medicine and Science, Los Angeles, CA; UC Irvine, Division of Basic and Clinical Immunology, Irvine, CA.

MGN-3, an arabinoxylan extracted from rice bran that is treated enzymatically with an extract from Shiitaki mushroom, is an effective biological response modifier that increases NK cell activity and potentiates the activity of conventional chemotherapeutic agents.

In this study, we investigated the effect of MGN-3 on death receptor-induced apoptosis in human leukemic HUT 78 cell line. HUT 78 cells were pretreated with MGN-3 and then were incubated with agonistic antibody against death receptor (Fas, CD95). Apoptosis was determined by propidium iodide technique using FACScan. Activation of caspase 3, caspase 8 and caspase 9 was determined by flow cytometry.

Mitochondrial membrane potential was measured with DIOC6 dye using FACScan. Expression of CD95 and BCl-2 were measured by flow cytometry. MGN-3 in a dose-dependent manner enhanced anti-CD95-induced apoptosis.

Increased cell death was correlated with increased depolarization of mitochondrial membrane potential and increased activation of caspase 3, caspase 8 and caspase 9. MGN-3 treatment had no effect on CD-95 and BCl-2 expression.

These results suggest that MGN-3 increases the susceptibility of cancer to undergo apoptosis mediated by death ligands, which may be relevant for anti-cancer activities.

MGN-3 was offered by Daiwa Pharmaceutical Co., Ltd. Tokyo, Japan.

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