当前位置： SCI文献检索 > CANCER CHEMOTHERAPY AND PHARMACOLOGY期刊下所有文献 > Actinomycin D and staurosporine, potent apoptosis inducers in vitro, are potentially effective chemotherapeutic agents against glioblastoma multiforme.

Actinomycin D and staurosporine, potent apoptosis inducers in vitro, are potentially effective chemotherapeutic agents against glioblastoma multiforme.

Abstract：

PURPOSE:Although chemotherapeutic protocols that include chloroethylnitrosoureas (CENUs), such as 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), have been a mainstay of treatment for glioblastomas, the clinical outcomes have been unsatisfactory. More effective chemotherapeutic protocols for these tumors will require clear delineation of more cytocidal and cytostatic chemotherapeutic drugs. METHODS AND RESULTS:In this study, we measured the cytocidal effects of ACNU, cisplatin, actinomycin D, and staurosporine, administered within their therapeutic dose ranges, in the treatment of glioblastoma cells. As assessed by WST-1 colorimetric assay, the number of viable cells decreased markedly in T98G cultures treated with actinomycin D or staurosporine, to less than 20% of the level in control cultures at 72 h, but did not decrease or even increased after 6 days of treatment with ACNU. After treatment with cisplatin for 5 days, cell viability decreased to 30% of control. As assessed by fluorescence microscopic examination of nuclear staining by Hoechst 33258 and by electron microscopy, the majority of dead cells treated with actinomycin D, staurosporine, or cisplatin had morphologic features of apoptosis. Caspase-3 activity increased more than 20-fold in cells treated with actinomycin D, staurosporine, or cisplatin but increased less than fivefold in ACNU-treated cells. In addition to caspase-3 activation, western blot analysis demonstrated cleavage of caspase-2 during the apoptotic process. These findings indicate that actinomycin D and staurosporine potently induce apoptosis, whereas ACNU exerts mainly a cytostatic rather than a cytocidal effect. CONCLUSION:Actinomycin D and staurosporine and their derivatives are potentially effective chemotherapeutic agents against glioblastoma cells at least in vitro.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Narita Y,Asai A,Kuchino Y,Kirino T

doi

10.1007/s002800050023

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

149-56

issue

eissn

0344-5704

issn

1432-0843

pii

00450149.280

journal_volume

pub_type

杂志文章

在线工具

Actinomycin D and staurosporine, potent apoptosis inducers in vitro, are potentially effective chemotherapeutic agents against glioblastoma multiforme.