Inhibition of Tumor Cell Invasion by Verapamil

KARIN H. YOHEM*, JOHN L. CLOTHIER, SANDRA L. MONTAGUE, ROSEMARY J. GEARY, ADRIAN L. WINTERS, MARY J.C. HENDRIX, DANNY R. WELCH

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Verapamil, a calcium channel antagonist, inhibits murine B16 melanoma and colon adenocarcinoma C26 tumor metastasis by altering platelet aggregation [Tsuruo, T., et al. (1985) Cancer Chemother. Pharmacol., 14:30–33]. However, the role of calcium homeostasis in regulating several biochemical pathways implicated in other steps of the meta‐static cascade suggests that calcium channel antagonists could also inhibit metastasis by other mechanisms. In this report, non‐toxic doses of verapamil reversibly decreased human A375M and C8161 melanoma cell invasion and metastasis in a dose‐dependent manner. Verapamil reduced cellular invasion and metastases by up to 96% (range 78–96%). Concomitantly, verapamil disrupts microtubule and microfilament organization and inhibits unidirectional cell migration but does not affect cellular adhesion to endothelial mono‐layers or reconstituted basement membranes. In addition, tumor cells treated with verapamil have a decrease in mRNA of type IV collagenase, a proteinase important in tumor cell degradation of basement membranes. Collectively, these data offer additional evidence regarding the mechanisms of action of verapamil as an anti‐metastatic agent.

Original languageEnglish (US)
Pages (from-to)225-233
Number of pages9
JournalPigment Cell Research
Volume4
Issue number5-6
DOIs
StatePublished - Dec 1991

Keywords

  • Cytoskeleton
  • Experimental metastases
  • Microfilaments
  • Microtubules
  • Type IV collagenase

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Plant Science
  • Developmental Biology
  • Clinical Biochemistry
  • Cell Biology

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