Effects of spin labeled derivatives of podophyllotoxin on cell cycle and macromolecular synthesis in human lymphoid leukemia Molt 4B cells.

Abstract

AIM:

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.

CONCLUSION:

GP4 and GP7 inhibit the proliferation of Molt 4B cells, but the mechanisms are different.

• Authors: J Z Wang, H Tsumura, K Shimura, X Tian, H Ito
• Journal: Zhongguo yao li xue bao = Acta pharmacologica Sinica (Zhongguo Yao Li Xue Bao) Vol. 19 Issue 6 Pg. 501-5 (Nov 1998) ISSN: 0253-9756 [Print] China
• PMID: 10437132 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• DNA, Neoplasm
• N-podophyllic acid-N''-(4-(2,2,6,6-tetramethyl-1-piperidinyloxy))thiosemicarbazide
• Neoplasm Proteins
• GP 7
• Etoposide
• Podophyllotoxin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Cycle
• Cell Division (drug effects)
• DNA, Neoplasm (biosynthesis)
• Etoposide (pharmacology)
• Humans
• Leukemia, Lymphoid (metabolism, pathology)
• Mitotic Index
• Neoplasm Proteins (biosynthesis)
• Podophyllotoxin (analogs & derivatives, pharmacology)
• Tumor Cells, Cultured