Antiproliferative effect in vitro and antitumor activity in vivo of brefeldin A

Edward A. Sausville, Kimberly L.K. Duncan, Adrian Senderowicz, Jacqueline Plowman, Paul A. Randazzo, Richard Kahn, Louis Malspeis, Michael R. Grever

Research output: Contribution to journalArticle

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 × 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.

Original languageEnglish (US)
Pages (from-to)52-58
Number of pages7
JournalCancer Journal from Scientific American
Volume2
Issue number1
StatePublished - Dec 1 1996

Keywords

  • Brefeldin A
  • Golgi
  • In vitro
  • In vivo
  • Melanoma
  • Prostate cancer
  • Protein secretion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Antiproliferative effect in vitro and antitumor activity in vivo of brefeldin A'. Together they form a unique fingerprint.

  • Cite this

    Sausville, E. A., Duncan, K. L. K., Senderowicz, A., Plowman, J., Randazzo, P. A., Kahn, R., Malspeis, L., & Grever, M. R. (1996). Antiproliferative effect in vitro and antitumor activity in vivo of brefeldin A. Cancer Journal from Scientific American, 2(1), 52-58.