Increased intracellular Ca2+ signaling caused by the antitumor agent helenalin and its analogues

Garth Powis, Alfred Gallegos, Robert T. Abraham, Curtis L. Ashendel, Leon H. Zalkow, Gerald B. Grindey, Rosanne Bonjouklian

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The antitumor sesquiterpene lactone helenalin, which is found in species of the plant genus Helenium, cause a marked potentiation of the increases in intracellular free Ca2+ concentration ([Ca2+]i) produced by mitogens such as vasopressin, bradykinin, and platelet-derived growth factor in Swiss mouse 3T3 fibroblasts. Removing external Ca2+ partly attenuated the increased [Ca2+]i response. caused by helenalin. The increased [Ca2+]i responses occurred at concentrations of helenalin that inhibited cell proliferation. At higher concentrations, helenalin inhibited the [Ca2+]i responses. No change in resting [Ca2+]i was caused by helenalin even at high concentrations. Other helenalin analogues also increased the [Ca2+]i response. Helenalin did not inhibit protein kinase C (PKC) and PKC appeared to play a minor role in the effects of helenalin on [Ca2+]i responses in intact cells. Studies with saponin-permeabilized HT-29 human colon carcinosarcoma cells indicated that helenalin caused an increased accumulation of Ca2+ into nonmitochondrial stores and that the potentiating effect of helenalin on mitogen-stimulated [Ca2+]i responses was due in part to an increase in the inositol-(1,4,5)-trisphosphate-mediated release of Ca2+ from these stores.

Original languageEnglish (US)
Pages (from-to)344-350
Number of pages7
JournalCancer chemotherapy and pharmacology
Volume34
Issue number4
DOIs
StatePublished - Jul 1994

Keywords

  • Helenalin
  • Intracellular Ca

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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