Effects of 3-substituted aryl oxindole(PH II-7) on cell cycle of tumor cells.
- Author:
Yao-hong TAN
1
;
Chun-zheng YANG
;
Jing QI
;
Jin-hong WANG
;
Cai-yun WANG
;
Hui PENG
Author Information
- Publication Type:Journal Article
- MeSH: 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; Proto-Oncogene Proteins c-myc; metabolism; Retinoblastoma Protein; metabolism
- From: Acta Pharmaceutica Sinica 2003;38(11):805-808
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo study the antitumor mechanism of 3-substituted aryl oxindole (PH II-7) and determine its effects on cell cycle distribution of tumor cells.
METHODSThe 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.
RESULTSPH 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.
CONCLUSIONPH II-7, a new anti-tumor agent, blocks the transition of cell cycle of tumor cells from G1 to S phase by inhibition CDK2.