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

The antitumor sesquiterpene lactone helenalin, which is found in species of the plant genus Helenium, caused 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 mou...

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Published in:Cancer chemotherapy and pharmacology 1994, Vol.34 (4), p.344-350
Main Authors: POWIS, G, GALLEGOS, A, ABRAHAM, R. T, ASHENDEL, C. L, ZALKOW, L. H, GRINDEY, G. B, BONJOUKLIAN, R
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Antineoplastic agents
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - pharmacology
Biological and medical sciences
Calcium - physiology
General aspects
Medical sciences
Mice
Pharmacology. Drug treatments
Protein Kinase C - drug effects
Sesquiterpenes - chemistry
Sesquiterpenes - pharmacology
Signal Transduction - drug effects
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Summary:The antitumor sesquiterpene lactone helenalin, which is found in species of the plant genus Helenium, caused 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 responses 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.
ISSN:0344-5704
1432-0843
DOI:10.1007/BF00686043