Effects of the bioreductive alkylating agent 2,3-bis(chloromethyl)-1,4-naphthoquinone on coupled mitochondria isolated from sarcoma 180 ascites cells.

Abstract

The effect of CMNQ was studied on mitochondria isolated from S-180 ascites tumor cells. It was found that the primary metabolic event upon addition of CMNQ to S-180 mitochondria was a stimulation of oxygen uptake. The oxygen utilization rate was maximized at about 50 nmoles CMNQ/mg protein; at doses higher than this, inhibition of respiration was observed relative to the stimulation of respiration produced by CCCP. It was also up to 50 nmoles CMNQ/mg protein. S-180 ATPase activity is stimulated maximally by 125 nmoles CMNQ/mg protein; at doses higher than this, slight inhibition of the ATPase activity relative to the stimulation produced by CCCP is seen. In vivo treatment of CMNQ to tumor bearing animals leads to a significant reduction of in vitro S-180 cellular respiration rates. The data presented in this work coupled with previously published reports involving CMNQ support the proposal for a mitochondrial level of action for this bioreductive alkylating antineoplastic agent.

• Authors: R E Biagini, R S Pardini, A J Lin, A C Sartorelli
• Journal: Cancer biochemistry biophysics (Cancer Biochem Biophys) Vol. 3 Issue 3 Pg. 129-34 ( 1979) ISSN: 0305-7232 [Print] England
• PMID: 162226 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Naphthoquinones
• Succinates
• 2,3-bis(chloromethyl)-1,4-naphthoquinone
• Carbonyl Cyanide m-Chlorophenyl Hydrazone
• Adenosine Diphosphate
• Adenosine Triphosphatases

Topics

• Adenosine Diphosphate (metabolism)
• Adenosine Triphosphatases (metabolism)
• Animals
• Carbonyl Cyanide m-Chlorophenyl Hydrazone (pharmacology)
• Kinetics
• Mice
• Mitochondria (drug effects, metabolism)
• Naphthoquinones (pharmacology)
• Oxidative Phosphorylation (drug effects)
• Oxygen Consumption (drug effects)
• Sarcoma 180 (metabolism)
• Succinates (metabolism)