Antiproliferative effect in vitro and antitumor activity in vivo of brefeldin A.
Cancer J Sci Am
; 2(1): 52-8, 1996.
Article
in En
| MEDLINE
| ID: mdl-9166499
ABSTRACT
PURPOSE:
An empiric in vitro screen of human tumor cell lines found brefeldin A inhibited the growth of immortalized human cell lines, with particular sensitivity to brefeldin in a series of immortalized melanoma cell lines and nonimmortalized prostate carcinoma explants. Brefeldin A alters the morphology and function of the Golgi apparatus, endosomal, and trans-Golgi compartments in different cell types. The studies presented here sought to obtain evidence of in vivo antitumor activity by brefeldin A.METHODS:
Antiproliferative activity was studied in prostate carcinoma cells in vitro using cell counts, protein, and viable stains. Activity was also studied in vivo against subcutaneous and subrenal capsule melanoma models.RESULTS:
Protracted exposures in vitro (between 24 and 72 hours) are necessary to cause persistent growth inhibition of immortalized PC3 prostate carcinoma cells. In human melanoma athymic mouse xenografts, brefeldin A showed antitumor activity in vivo when given 16 to 64 mg/kg/injection intraperitoneally q 7 h x 2, daily for 5 days. Activity was also observed in the intraperitoneal LOX IMVI (65%-100% increase in life span, with 17%-50% day 60 survivors); early-stage subcutaneous LOX IMVI and SK-MEL-5 (86%-100% growth inhibition), and subrenal capsule SK-MEL-5 and M19-MEL models.CONCLUSIONS:
Brefeldin A possesses noteworthy antitumor activity in vivo and antiproliferative effects in vitro in certain cell types. Strategies to allow protracted exposure of tumor cells to brefeldin A while preserving a therapeutic index are needed to assess the clinical potential of brefeldin A.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Synthesis Inhibitors
/
Brefeldin A
/
Cell Proliferation
/
Neoplasms, Experimental
/
Antineoplastic Agents
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cancer J Sci Am
Journal subject:
NEOPLASIAS
Year:
1996
Document type:
Article
Affiliation country:
United States