The Plasmodium circumsporozoite protein, a novel NF-κB inhibitor, suppresses the growth of SW480.
The blocking of NF-κB activation is a promising strategy for the treatment of colorectal cancer. The circumsporozoite protein (CSP), a key component of the sporozoite stage of the malaria parasite, was recently reported to block NF-κB activation in hepatocytes. Thus, we investigated the effect of the CSP on the growth of the human colon cancer cell line, SW480. We demonstrated that transfection with a recombinant plasmid expressing CSP inhibited the proliferation of SW480 in a dose-dependent manner and induced the apoptosis of SW480. A NF-κB gene reporter assay showed that both the CSP and its nuclear localization signal (NLS) motif could equally suppress the activation of NF-κB following the stimulation with human recombinant TNF-α in the SW480. Furthermore, western blot analysis indicated that NLS did not affect the phosphorylation and degradation of IκB, but could sharply inhibit the nuclear translocation of NF-κB in TNF-α stimulated SW480. Hence, our data suggest that the CSP might be explored as a new NF-κB inhibitor for the treatment of colorectal cancer.
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing, 400038, People's Republic of China.
Yan
Y
Ding
Xiaobing
X
Huang
Taiping
T
Liu
Yong
Y
Fu
Zhangping
Z
Tan
Hong
H
Zheng
Taoli
T
Zhou
Jigang
J
Dai
Wenyue
W
Xu
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; C041595:circumsporozoite protein, Protozoan