Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells

K. Sato, J. Ishizuka, C. W. Cooper, D. H. Chung, T. Tsuchiya, T. Uchida, S. Rajaraman, Courtney Townsend, J. C. Thompson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Calcium, which binds to calmodulin inside the cell, is an important mediator of various intracellular processes, including cell proliferation. We speculated that blockade of Ca2+ influx into the cells by Ca2+-channel blockers, such as phenytoin and verapamil, might affect the Ca2+-calmodulin pathway leading to suppression of cell growth. In this study, we examined the effect of phenytoin and verapamil on growth of two human pancreatic cancer cell lines, MIA PaCa-2 and CAV, in vitro and in vivo. Both phenytoin and verapamil inhibited growth of the two cell lines in a dose-dependent fashion. Phenytoin and verapamil each significantly prolonged doubling time of MIA PaCa-2 and the combination of the two drugs acted synergistically. The activity of ornithine decarboxylase, which is a rate-limiting enzyme of the polyamine pathway that is closely related to cell proliferation, was significantly inhibited by both drugs in a time-dependent fashion. Phenytoin, but not verapamil, inhibited growth of MIA PaCa-2 tumors xenotransplanted into nude mice, whereas both phenytoin and verapamil inhibited the growth of CAV tumors. Since phenytoin and verapamil are known to have fewer side effects than conventional antineoplastic drugs, these results suggest their possible use in novel therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)193-202
Number of pages10
JournalPancreas
Volume9
Issue number2
StatePublished - 1994

Fingerprint

Calcium Channel Blockers
Phenytoin
Verapamil
Pancreatic Neoplasms
Growth
Calmodulin
Cell Proliferation
Cell Line
Ornithine Decarboxylase
Polyamines
Drug Combinations
Nude Mice
Antineoplastic Agents
Neoplasms
Calcium
Enzymes
Pharmaceutical Preparations

Keywords

  • Calcium
  • Phenytoin
  • Verapamil

ASJC Scopus subject areas

  • Endocrinology
  • Gastroenterology

Cite this

Sato, K., Ishizuka, J., Cooper, C. W., Chung, D. H., Tsuchiya, T., Uchida, T., ... Thompson, J. C. (1994). Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells. Pancreas, 9(2), 193-202.

Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells. / Sato, K.; Ishizuka, J.; Cooper, C. W.; Chung, D. H.; Tsuchiya, T.; Uchida, T.; Rajaraman, S.; Townsend, Courtney; Thompson, J. C.

In: Pancreas, Vol. 9, No. 2, 1994, p. 193-202.

Research output: Contribution to journalArticle

Sato, K, Ishizuka, J, Cooper, CW, Chung, DH, Tsuchiya, T, Uchida, T, Rajaraman, S, Townsend, C & Thompson, JC 1994, 'Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells', Pancreas, vol. 9, no. 2, pp. 193-202.
Sato K, Ishizuka J, Cooper CW, Chung DH, Tsuchiya T, Uchida T et al. Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells. Pancreas. 1994;9(2):193-202.
Sato, K. ; Ishizuka, J. ; Cooper, C. W. ; Chung, D. H. ; Tsuchiya, T. ; Uchida, T. ; Rajaraman, S. ; Townsend, Courtney ; Thompson, J. C. / Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells. In: Pancreas. 1994 ; Vol. 9, No. 2. pp. 193-202.
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