Effects of spin labeled derivatives of podophyllotoxin on cell cycle and macromolecular synthesis in human lymphoid leukemia Molt 4B cells.
OBJECTIVE
To examine the effect of the spin labeled derivatives of podophyllotoxin, N-podophyllic acid-N"-[4-(2,2,6,6-tetramethyl-1-piperidinyloxy)] thiosemicarbazide (GP4) and 4-[4"-(2",2",6",6"-tetramethyl-1"-piperidinyloxy) amino]-4'-demethylepipodophyllotoxin (GP7) on the cell cycle and macromolecular synthesis of human lymphoid leukemia Molt 4B cells in vitro.


METHODS
MTT assay, 3H incorporation, and flow cytometer were used.


RESULTS
GP4, GP7, and etoposide 0.02-100 mmol.L-1 cultured for 48 h inhibited the proliferation of human lymphoid leukemia Molt 4B cells. IC50 values of GP4, GP7, and etoposide were 0.11, 4.7, and 1.6 mmol.L-1, respectively. DNA and protein syntheses were obviously suppressed by GP4, GP7, and etoposide 10 mmol.L-1 for 48 h. After Molt 4B cells were treated with GP4, GP7, and etoposide 10 mmol.L-1 for 6 and 12 h, the mitotic index was increased by GP4 and reduced by GP7 and etoposide. According to flow cytometric BrdU/DNA analysis, GP4 slightly retarded S phase and mainly arrested cell cycle progression in G2/M phase, whereas GP7 similar to etoposide induced cells accumulated at S phase and retarded the cells in G2 phase.


CONCLUSIONS
GP4 and GP7 inhibit the proliferation of Molt 4B cells, but the mechanisms are different.
Wang
J Z
JZ
Department of Biochemistry, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, China. biochem@public3.bta.net.cn
Tsumura
H
H
Shimura
K
K
Tian
X
X
Ito
H
H
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000473:pathology*; D008940:Mitotic Index; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; C400083:N-podophyllic acid-N''-(4-(2,2,6,6-tetramethyl-1-piperidinyloxy))thiosemicarbazide; D009363:Neoplasm Proteins; C071346:GP 7; D005047:Etoposide; D011034:Podophyllotoxin