[Antitumor activity of 4-(4''-(2'',2'',6'',6''-tetramethyl-1''-piperidinyoxy)amino)-4'- demethyl epipodophyllotoxin in vitro].
The antitumor activity of a new podophyllotoxin spin-labeled derivative, 4-(4''-(2'',2'',6'',6''-tetramethyl-1''-+piperidinyoxy)amino)-4'- demethylepipodophyllotoxin (GP-7) First synthesized by us, was studied in vitro. It was found that the proliferation of SGC-7901 cells was markedly inhibited by GP-7 depending the concentration and exposure time. At concentration of 0.04-100 mg/L, the inhibition rates were 15.5-92.6% ID50 was 0.42 mg/L. After exposure to GP-7 greater than 0.5 mg/L for 24, 48, 72 and 96 h, the inhibition rates of cells were 25.1, 49.0, 71.4 and 84.9% respectively. The dose-response curve of GP-7 on SGC-7901 cell was similar to that of etoposide (VP-16). The colony formation of SGC-7901 cell was also inhibited by GP-7 in a concentration dependent fashion with ID50 1.63 mg/L. At concentrations of 0.1-0.5 mg/L, the inhibitory effects were stronger than that of VP-16. GP-7 decreased the mitotic index (MI) of SGC-7901 cell and had no effect on microtubule assembly and disassembly in vitro, which suggested that GP-7 did not act on M phase.
Jia
Z P
ZP
Department of Pharmacology, Lanzhou Medical College, China.
Zhang
P Y
PY
Liang
Z D
ZD
Wang
Y G
YG
Chen
Y Z
YZ
Li
J X
JX
Tian
X
X
D000970:Antineoplastic Agents; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000187:drug effects; D008940:Mitotic Index / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D008869:Microtubule-Associated Proteins; C071346:GP 7; D005047:Etoposide; D011034:Podophyllotoxin