title: Pharmacokinetics, biodistribution and antitumour effects of Sclerotium rolfsii lectin in mice.
abstract: Sclerotium rolfsii lectin (SRL) is a lectin isolated from the fungus Sclerotium rolfsii and has exquisite binding specificity towards the oncofetal Thomsen-Friedenreich antigen (TF-Ag; Galβ1-3GalNAcα-O-Ser/Thr) and its derivatives. Previous studies have shown that SRL inhibits the proliferation of human colon, breast and ovarian cancer cells in vitro and suppresses tumour growth in mice when introduced intratumourally. The present study assessed the effect of SRL on tumour growth when introduced intraperitoneally in BALB/c nude mice and investigated the pharmacokinetics and biodistribution of SRL in Swiss albino mice. When 9 doses of SRL (30 mg/kg body weight/mice) was administered to BALB/c nude mice bearing human colon cancer HT-29 xenografts, a substantial reduction in tumour size was observed. A 35.8% reduction in tumour size was noted in the treated animals after 17 days. SRL treatment also inhibited angiogenesis, and the tumours from the treated animals were observed to carry fewer blood vessels and express less angiogenesis marker protein CD31, than that from the control animals. Pharmacokinetics and biodistribution analysis revealed that SRL was detected in the serum after 1 h and its level peaked after 24 h. SRL was not detected in any of the organs apart from the kidney where a trace amount was detected after 24 h of SRL injection. No significant changes were observed in any of the biochemical parameters tested including SGOT, SGPT, LDH, CREAT and BUN in the SRL-treated mice compared to these levels in the controls. This suggests that SRL has good potential to be developed as a therapeutic agent for cancer treatment and warrant further investigations in vivo and subsequent clinical trials.
authors.affiliation: Department of Studies in Biochemistry, Karnatak University, Dharwad 580003, India.
authors.forename: S
authors.initials: S
authors.lastname: Anupama
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410210, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Laha
authors.affiliation: Department of Studies in Biochemistry, Karnatak University, Dharwad 580003, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410210, India.
authors.forename: Kamal
authors.initials: K
authors.lastname: Pathak
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410210, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bane
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410210, India.
authors.forename: Arvind D
authors.initials: AD
authors.lastname: Ingle
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410210, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Gota
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410210, India.
authors.forename: Rajiv D
authors.initials: RD
authors.lastname: Kalraiya
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Lu-Gang
authors.initials: LG
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Rhodes
authors.affiliation: Department of Studies in Biochemistry, Karnatak University, Dharwad 580003, India.
authors.forename: Bale M
authors.initials: BM
authors.lastname: Swamy
authors.affiliation: Department of Studies in Biochemistry, Karnatak University, Dharwad 580003, India.
authors.forename: Shashikala R
authors.initials: SR
authors.lastname: Inamdar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001487:Basidiomycota / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D005656:Fungal Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D019073:HT29 Cells; D006801:Humans; D037102:Lectins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005656:Fungal Proteins; D037102:Lectins; D019408:Platelet Endothelial Cell Adhesion Molecule-1