Carcinogenesis response modulation induced by gelonin encapsulated in liposome.
The effectiveness of gelonin to arrest protein synthesis, thereby limiting the growth of cancer cells was studied by encapsulating it into liposomes. The protein was extracted from the seeds of Indian plant Gelonium multiflorum by ammonium sulfate precipitation and purified using cation-exchange and gel-filtration chromatography. Biological activity of purified gelonin was determined using a rabbit reticulocyte lysate assay in the cell-free translational experiments. Gelonin was encapsulated in conventional liposomes prepared by the dry film method in order to retain biological activity of the entrapped protein. Carcinogenesis was induced in Swiss albino mice by intravenous administration of DBN (10 mg kg(-1) body weight) at weekly intervals. Marker enzyme assays (GGT, AChE, and GST), GSH levels, cell proliferation assay, hepatocyte DNA analysis, histological examination of micro sections of liver tissues were parameters used to monitor carcinogenesis induction, and regression in mice. From the in vitro experiments conducted, it was observed that gelonin upon its encapsulation into liposome, resulted in significant destruction of the transformed liver cells by its cytotoxic effects that arrest protein synthesis. Various parameters studied to monitor regression also suggested mass cell destruction to liver upon administration of liposomal gelonin in mice exposed to DBN.
Alam
Anis
A
Immunology Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong, Meghalaya, India. a_alam51@yahoo.com
Nakhuru
K S
KS
Singha
L I
LI
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D015197:Carcinogenicity Tests; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D022781:Hepatocytes / Q000187:drug effects; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008970:Molecular Weight; D012157:Mononuclear Phagocyte System / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology*
D015415:Biomarkers; D008081:Liposomes; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D004247:DNA; D001973:Bromodeoxyuridine