The TF-antigen binding lectin from Sclerotium rolfsii inhibits growth of human colon cancer cells by inducing apoptosis in vitro and suppresses tumor growth in vivo.
Glycan array analysis of Sclerotium rolfsii lectin (SRL) revealed its exquisite binding specificity to the oncofetal Thomsen-Friedenreich (Galβ1-3GalNAcα-O-Ser/Thr, T or TF) antigen and its derivatives. This study shows that SRL strongly inhibits the growth of human colon cancer HT29 and DLD-1 cells by binding to cell surface glycans and induction of apoptosis through both the caspase-8 and -9 mediated signaling. SRL showed no or very weak binding to normal human colon tissues but strong binding to cancerous and metastatic tissues. Intratumor injection of SRL at subtoxic concentrations in NOD-SCID mice bearing HT29 xenografts resulted in total tumor regression in 9 days and no subsequent tumor recurrence. As the increased expression of TF-associated glycans is commonly seen in human cancers, SRL has the potential to be developed as a therapeutic agent for cancer.
Department of Studies in Biochemistry, Karnatak University, Dharwad-580 003, India. pinkisri2001@yahoo.co.in
Shashikala R
SR
Inamdar
Mohammed Azharuddin
MA
Savanur
Sachin M
SM
Eligar
Vishwanath B
VB
Chachadi
Nagaraja N
NN
Nagre
Chen
C
Chen
Monica
M
Barclays
Aravind
A
Ingle
Praveen
P
Mahajan
Anita
A
Borges
Padma
P
Shastry
Rajiv D
RD
Kalraiya
Bale M
BM
Swamy
Jonathan M
JM
Rhodes
Lu-Gang
LG
Yu
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001203:Ascomycota / Q000737:chemistry*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007267:Injections; D037102:Lectins / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D037102:Lectins; D011134:Polysaccharides; C016467:Thomsen-Friedenreich antigen; D053181:Caspase 8; D053453:Caspase 9