Antitumor and proapoptotic effect of Abrus agglutinin derived peptide in Dalton's lymphoma tumor model

Abrus agglutinin peptide fractions obtained from 10kD molecular weight cut off membrane permeate (10 kMP), was shown to have selective anti proliferative activity on several tumor cell lines with induction of apoptosis through mitochondrial pathway. The present study was designed to evaluate acute general toxicity and in vivo therapeutic effectiveness of 10kMPP in Dalton's lymphoma (DL) mice model. The acute toxicity like body weight, peripheral blood cell count, lympho-hematological and biochemical parameters remained unaffected with 1 mg/kg body weight and lower of 10kMPP. The in vivo antitumor study indicated that there were 27%, 58.5% and 84.5% reduction in DL cell survival in 100, 200 and 500 mu g/kg body weight of 10 kMPP, respectively. Analysis of the growth inhibitory mechanism in DL cells revealed nuclear fragmentation and condensation with appearance of the sub G0/G1 peak is indicative of apoptosis. Further, the Western blotting showed apoptosis was mediated by reduction in ratio of Bcl-2 and Bax protein expression, and activation of caspase-3 through release of cytochrome-c in DL cells. Kaplan-Meier survival analysis showed an effective antitumor response (53 ILS%) with dose of 500 mu g/kg body weight. Our result showed that the novel peptides present in Abrus agglutinin possess potent antitumor properties which need to be further explored. (c) 2008 Elsevier Ireland Ltd. All rights reserved.