Glycine- and proline-rich glycoprotein regulates the balance between cell proliferation and apoptosis for ACF formation in 1,2-dimethylhydrazine-treated A/J mice.
The objective of this study was to investigate the chemopreventive potentials of glycine- and proline-rich glycoprotein (SNL glycoprotein, 150-kDa) isolated from Solanum nigrum Linne on formation of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg) in A/J mice. Administration of SNL glycoprotein inhibited phosphorylation of extracellular signal-regulated kinase (ERK), expression of colonic proliferating cell nuclear antigen (PCNA), and frequency of colonic ACF in DMH-stimulated mice colon carcinogenesis. In addition, SNL glycoprotein increased expression of cyclin-dependent kinase inhibitors (p21(WAF/Cip1) and p27(Kip1)), whereas reduced expression of precursor form of apoptosis-related proteins [pro-caspase-3 and pro-poly(ADP-ribose)polymerase (PARP)] in the mice. Interestingly, the results in this study revealed that SNL glycoprotein has suppressive effects on activity of nuclear factor-kappa B (NF-kappaB), whereas it has stimulatory effect on the expression of p53, accompanying inhibitory effects on expression of NF-kappaBp50, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha in DMH-stimulated ACF formation. Also, SNL glycoprotein has inhibitory effects on the formation of thiobarbituric acid reactive substances (TBARS), on the production of inducible nitric oxide (NO), and on the release of lactate dehydrogenase (LDH) in the mice plasma. Collectively, our findings in this study suggest that SNL glycoprotein has chemopreventive activity via modulation of cell proliferation and apoptosis in DMH-treated A/J mice.
Lee
Sei-Jung
SJ
Molecular Biochemistry Laboratory, Biotechnology Research Institute, Chonnam National University, 300 Yongbong-Dong, Kwang-ju, 500-757, South Korea.
Lim
Kye-Taek
KT
D019813:1,2-Dimethylhydrazine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D049109:Cell Proliferation; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005998:Glycine / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000097:blood; D011392:Proline / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017931:DNA Primers; D006023:Glycoproteins; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D011392:Proline; D007770:L-Lactate Dehydrogenase; D019813:1,2-Dimethylhydrazine; D005998:Glycine