[Effects of 3-substituted aryl oxindole(PH II-7) on cell cycle of tumor cells].

Abstract

AIM:

To study the antitumor mechanism of 3-substituted aryl oxindole (PH II-7) and determine its effects on cell cycle distribution of tumor cells.

METHODS:

The cell cycle distributions were determined with FACS. The cell cycle regulation-related proteins of K562 lysates were analyzed with Western Blot. The inhibition of PH II-7 on DNA synthesis of tumor cells were estimated though 3H-thymidine incorporation and the tyrosine kinase activity of EGFR of A431 lysates was measured with ELISA.

RESULTS:

PH II-7 effected cell cycle distribution of several tumor cells, including multidrug resistant tumor cell lines, and accumulation of cells in the G0-G1 stages was observed. The cell cycle regulation-related proteins CDK2, Rb and c-myc were inhibited by PH II-7 in a dose dependent manner, whereas the expression of CyclinE was increased after exposure to PH II-7. Furthermore, PH II-7 2.0 mg.L-1 was shown to inhibit the incorporation of 3H-thymidine into DNA, and 21.89%-41.29% of the PTK activity of EGFR in A431 lysates was inhibited by PH II-7 2-8 mg.L-1 in a dose-dependant manner.

CONCLUSION:

PH II-7, a new anti-tumor agent, blocks the transition of cell cycle of tumor cells from G1 to S phase by inhibition CDK2.

• Authors: Yao-hong Tan, Chun-zheng Yang, Jing Qi, Jin-hong Wang, Cai-yun Wang, Hui Peng
• Journal: Yao xue xue bao = Acta pharmaceutica Sinica (Yao Xue Xue Bao) Vol. 38 Issue 11 Pg. 805-8 (Nov 2003) ISSN: 0513-4870 [Print] China
• PMID: 14991989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cell Cycle Proteins
• Cyclin E
• DNA, Neoplasm
• Indoles
• Oxindoles
• Proto-Oncogene Proteins c-myc
• Retinoblastoma Protein
• 2-oxindole
• CDC2-CDC28 Kinases
• CDK2 protein, human
• Cyclin-Dependent Kinase 2

Topics

• Antineoplastic Agents (pharmacology)
• CDC2-CDC28 Kinases (metabolism)
• Cell Cycle (drug effects)
• Cell Cycle Proteins (metabolism)
• Cyclin E (metabolism)
• Cyclin-Dependent Kinase 2
• DNA, Neoplasm (biosynthesis)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Humans
• Indoles (chemical synthesis, pharmacology)
• K562 Cells (pathology)
• Oxindoles
• Proto-Oncogene Proteins c-myc (metabolism)
• Retinoblastoma Protein (metabolism)