Apoptotic toxicity of destruxin B in human non-Hodgkin lymphoma cells

Abstract

Destruxins are fungal toxins used as insecticides. Recent reports demonstrated the potential anti-cancer activities of destruxin B (DB). This study is to discover the effects of DB in lymphoma. Flow cytometry and Western blotting were used to analyze apoptosis and protein expression, respectively, in Toledo human non-Hodgkin lymphoma cells in response to DB. Administration of DB, induced apoptosis via death receptor pathway activating Fas associated death domain (FADD), caspase 8 and caspase 3, and suppressed the cell growth. In addition, DB alterated mitochondrial membrane potential by increasing the expressions of tBid and Bax, but decreasing the levels of Bcl-2, resulting in the release of apoptosis-inducing factor (AIF). In conclusion, apoptosis of human non-Hodgkin lymphoma cells in response to DB is induced through the death receptor pathway and involves an alteration of the mitochondrial membrane potential. These findings may aid the development of novel treatment of non-Hodgkin lymphoma.

Keywords: 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide; AIF; Apaf; Apoptosis; DB; Death receptor pathway; Destruxin B; FACS; FADD; FITC; Fas associated death domain; JC-1; Mitochondrial membrane potential; Non-Hodgkin lymphoma; PI; apoptosis-inducing factor; apoptotic protease-activating factor; destruxin B; fluorescein isothiocyanate; fluorescence-activated cell sorting; propidium iodide.