Document Detail


MST-16, a novel bis-dioxopiperazine anticancer agent, ameliorates doxorubicin-induced acute toxicity while maintaining antitumor efficacy.
MedLine Citation:
PMID:  10632373     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MST-16 [4,4-1,2-(ethanediyl)bis(1-isobutoxycarbonyl-oxy-methyl-2,6-pipera zinedione)], recently approved as an oral anticancer drug for clinical use in Japan, was evaluated as a chemotherapeutic agent in combination with doxorubicin (DOX) in vitro and in vivo. Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and murine Colon 26 and human KATO III adenocarcinoma cells were used. The combination index derived from these cytotoxic values indicated a synergistic interaction between DOX and MST-16 or its active metabolite, ICRF-154 (1,1'-ethylenedi-3,5-dioxopiperazine). A maximal tolerated dose of DOX administered to female BALB/c mice bearing a solid Colon 26 tumor resulted in severe body weight loss and diarrhea, but a limited tumor growth delay (1.8 days). However, when combined with an oral dose of MST-16, DOX-induced body weight loss and diarrhea were significantly ameliorated, and an additive tumor growth delay (8.7 days) was obtained. The LD50 of DOX administered i.p. to control female BALB/c mice increased more than 1.5-fold when combined with MST-16. Thus, MST-16 ameliorates DOX-induced acute toxicity while maintaining antitumor efficacy. These results indicate that MST-16 may be effective chemotherapy for cancer patients when combined with DOX.
Authors:
M Yoshida; Y Maehara; K Sugimachi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  5     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-02-14     Completed Date:  2000-02-14     Revised Date:  2006-04-24    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4295-300     Citation Subset:  IM    
Affiliation:
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / pharmacology*,  toxicity*
Antineoplastic Agents / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Digestive System / drug effects
Doxorubicin / pharmacology*,  toxicity*
Female
Humans
Lethal Dose 50
Mice
Mice, Inbred BALB C
Neoplasms, Experimental / drug therapy,  pathology
Piperazines / pharmacokinetics,  pharmacology*
Prodrugs / pharmacokinetics
Razoxane / analogs & derivatives,  pharmacology
Survival Analysis
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antineoplastic Agents; 0/Piperazines; 0/Prodrugs; 1506-47-4/1,2-bis(3,5-dioxopiperazin-1-yl)ethane; 21416-87-5/Razoxane; 23214-92-8/Doxorubicin; 98631-95-9/sobuzoxane

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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