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Menadione: spectrum of anticancer activity and effects on nucleotide metabolism in human neoplastic cell lines.

Abstract：

:The spectrum of cytotoxicity of menadione (MD) was examined in a panel of human cancer cell lines. MD was equipotent against multidrug-resistant and parental leukemia cell lines with IC50 values of 13.5 +/- 3.6 and 18 +/- 2.4 microM respectively. A cervical carcinoma cell line resistant to the antimetabolite, methotrexate (MTX), was as sensitive to MD as its parental cell line. The interactions of fifteen clinically utilized anticancer drugs with MD were examined in vitro and the majority were found to be additive, with four agents exhibiting synergism and one agent exhibiting antagonism. MD inhibited the incorporation of radioactive thymidine, uridine and amino acids into DNA, RNA and protein, respectively, in three human cancer cell lines. Some possible reasons for the inhibition of DNA synthesis including effects of MD on intracellular deoxyribonucleoside triphosphate pools were examined and ruled out. Although results from previous studies using rat hepatocytes suggested that mitochondria may be a target of MD, no significant effect of this compound on total intracellular adenosine triphosphate (ATP) pools in human cancer cell lines was observed. Collectively, these in vitro results demonstrate that MD possesses a broad spectrum of anticancer activity and suggest the potential utility of this agent in cancer therapy. Future studies directed at elucidation of the mechanism of MD action in human cancer cells are warranted and are under study.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Nutter LM,Cheng AL,Hung HL,Hsieh RK,Ngo EO,Liu TW

doi

10.1016/0006-2952(91)90099-q

subject

Has Abstract

pub_date

1991-05-01 00:00:00

pages

1283-92

issue

9

eissn

0006-2952

issn

1873-2968

pii

0006-2952(91)90099-Q

journal_volume

41

pub_type

杂志文章

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