Effects of spin labeled derivatives of podophyllotoxin on cell cycle and macromolecular synthesis in human lymphoid leukemia Molt 4B cells
Wang, J.Z.; Tsumura, H.; Shimura, K.; Tian, X.; Ito, H.
Zhongguo Yao Li Xue Bao 19(6): 501-505
1998
ISSN/ISBN: 0253-9756 PMID: 10437132 Document Number: 496562
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. MTT assay, 3H incorporation, and flow cytometer were used. 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. GP4 and GP7 inhibit the proliferation of Molt 4B cells, but the mechanisms are different.