INDUCTION OF ENDONUCLEOLYTIC DNA FRAGMENTATION AND APOPTOSIS BY THE DUOCARMYCINS

被引：54

作者：

WRASIDLO, W ^{[1
]}

JOHNSON, DS ^{[1
]}

BOGER, DL ^{[1
]}

机构：

[1] SCRIPPS RES INST, DEPT CHEM, LA JOLLA, CA 92037 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1994年 / 4卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(01)80168-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The duocarmycins are exceptionally potent, naturally occurring antitumor antibiotics related to (+)-CC-1065. Short term exposure (1-4 h) of Molt-4 or L-1210 cells to the agents produced internucleosomal DNA fragmentation in approximately 200 base-pair multiples and at dose levels as low as 100 pM produced morphological changes characteristic of programmed cell death. These results were associated with strong inhibition of suspension culture growth and clonogenic survival suggesting that at physiologically relevant concentrations the agents induced cell death by a target cell activated pathway. Presumably, this is the consequence of the sequence selective alkylation of DNA by the duocarmycins potentially at internucleosomal sites, followed by intracellular signalling with activation of endonucleases, to trigger the apoptotic cell death mechanism.

引用

页码：631 / 636

页数：6

共 65 条

[11] DUOCARMYCIN PYRINDAMYCIN DNA ALKYLATION PROPERTIES AND IDENTIFICATION, SYNTHESIS, AND EVALUATION OF AGENTS INCORPORATING THE PHARMACOPHORE OF THE DUOCARMYCIN PYRINDAMYCIN ALKYLATION SUBUNIT - IDENTIFICATION OF THE CC-1065-DUOCARMYCIN COMMON PHARMACOPHORE [J].