Antiproliferative and cancer-chemopreventive properties of sulfated glycosylated extract derived from Leucaena leucocephala
1 Department of Biochemistry, Cancer Biology Laboratory, Nobel Project, National Research Center, Cairo, Egypt 2 Department of Natural and Microbial Products Chemistry, National Research Centre, Cairo, Egypt 3 Department of Molecular biology, Genetic Engineering and Biotechnology Research Institute, Minofyia University, Egypt
Amira M Gamal-Eldeen Department of Biochemistry, Cancer Biology Laboratory, Nobel Project, National Research Center, Cairo Egypt E-mail: [email protected]
This work aimed to prove that simple chemical modification could provide new cancer chemopreventive and/or anticancer properties to the inactive extracted polysaccharide derived from Leucaena leucocephala . Polysaccharides were extracted from Leucaena leucocephala seeds and its 2,4-pentanedione-treated derivative (glycosylated form) was prepared, which is further sulphated to give sulphated glycosylated form. Estimation of their anti-initiation activity, modulation of carcinogen metabolism, was indicated by the inhibition cytochrome P450 1A (CYP1A) and the induction of glutathione-S-transferases (GSTs). Anti-proliferation activity was investigated by MTT assay against human hepatocarcinoma (HepG2), breast carcinoma (MCF-7) and lymphoblastic leukemia (1301). Apoptosis/necrosis and cell cycle were analyzed by flow cytometry. The results revealed that glycosylated form inhibited both CYP1A and GSTs, while sulphated glycosylated form not only inhibited CYP1A, but also induced the GSTs. Unlike GE, sulphated glycosylated form possessed a significant anti-proliferative activity against different cell lines. Analysis of HepG2 cell cycle phases demonstrated that glycosylated form led to a delay of G2/M-phase, while sulphated glycosylated form led to a concomitant arrest in S- and G2/M-phases. Investigation of apoptosis/necrosis ratio demonstrated that both of glycosylated form and sulphated glycosylated form induced HepG2 cell death by necrosis, but not apoptosis. Unmodified crude extract was neither active as cancer chemopreventive nor as anti-proliferative. In conclusion, chemical modification of Leucaena gum induced its cancer chemopreventive and anti-proliferative activities.