Increased intracellular Ca2+ signaling caused by the antitumor agent helenalin and its analogues.
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| Abstract |
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.
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| Authors | G Powis, A Gallegos, R T Abraham, C L Ashendel, L H Zalkow, G B Grindey, R Bonjouklian |
| Journal | Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 34 Issue 4 Pg. 344-50 ( 1994) ISSN: 0344-5704 [Print] Germany |
| PMID | 8033301 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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