PpGalNacT2 participating in vanadium-induced HL-60 cell differentiation.
The current study demonstrates vanadium plays the role of antitumor, and its antitumor effect is dosage-dependent. N-acetyl-galactosamine-transferase 2 (polypeptide: N-acetyl-α-galactosaminyl-transferases 2, ppGalNAc-T2) is a member of ppGalNAcTs (polypeptide: N-acetyl-α-galactosaminyl-transferases) family, which proves to play a vital role in the tumor emergence and development process. In this study, we focused on ppGalNAc-T2 and vanadium and aimed to determine whether ppGalNAc-T2 is correlated with vanadium's antitumor effect. We discovered that ppGalNAc-T2 changed with the variation of HL-60 cell growth induced by vanadium at mRNA level. Peanut agglutinin (PNA) is an exogenous lectin. PpGalNacT2 can be indirectly recognized by PNA. By means of flow cytometry and immunofluorescent staining, we found the deviation of PNA binding increased significantly at high concentration vanadium. Then we docked one of the possible compound substances of vanadium onto the body, VO(3) (molecular formula O(13)V(4), partial vanadate tetramer) and ppGalNAcT2, and simulated them via molecular dynamics, which showed that VO(3) may inhibit the activity of the enzyme by stemming conformational changes of a key loop of ppGalNAcT2. To sum up, our results suggested that ppGalNacT2 participated in vanadium induced HL-60 cell differentiation, which might be able to provide a new mechanism of vanadium's antitumor effect.
Gao
Yuan
Y
Department of Biochemistry and Molecular Biology, Soochow University, Suzhou, 215123 Jiangsu, People's Republic of China.
Tu
You Bin
YB
Guo
Yi
Y
Yang
Ling Yan
LY
Guo
Xiang Hong
XH
Xu
Lan
L
Xu
Zheng Rong
ZR
Wu
Shi Liang
SL
D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005453:Fluorescence; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008958:Models, Molecular; D017350:N-Acetylgalactosaminyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019887:Peanut Agglutinin / Q000378:metabolism; D018583:Pliability / Q000187:drug effects; D011134:Polysaccharides / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014639:Vanadium / Q000494:pharmacology*; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D016650:Fluorescein-5-isothiocyanate; D037102:Lectins; D017350:N-Acetylgalactosaminyltransferases; D019887:Peanut Agglutinin; D011134:Polysaccharides; D012333:RNA, Messenger; D014639:Vanadium; D000097763:Polypeptide N-acetylgalactosaminyltransferase