Tetrandrine and thapsigargin release arachidonic acid from cells in culture and stimulate prostacyclin production in rat liver cells, but may do so by different pathwaysReport as inadecuate




Tetrandrine and thapsigargin release arachidonic acid from cells in culture and stimulate prostacyclin production in rat liver cells, but may do so by different pathways - Download this document for free, or read online. Document in PDF available to download.

BMC Pharmacology

, 5:12

First Online: 24 June 2005Received: 26 January 2005Accepted: 24 June 2005

Abstract

BackgroundTetrandrine inhibits tumor cell proliferation and demonstrates chemoprevention in cancer models. Speculation on the association between its effects on K and Ca channels and cancer chemoprevention has been made. Thapsigargin also affects K and Ca conductance. Thapsigargin, however, is a weak tumor promoter in the two-stage model of mouse skin carcinogenesis, yet it can induce apoptosis in androgen-independent prostatic cancer cells. I have postulated that arachidonic acid release from cells in culture is associated with cancer chemoprevention. The effects of tetrandrine and thapsigargin on arachidonic acid release from human colon carcinoma and rat liver cells and prostacyclin production by rat liver cells are compared in the current studies.

ResultsTetrandrine and thapsigargin stimulate arachidonic acid release from human colon carcinoma and rat liver cells and prostacyclin production in rat liver cells. The stimulation by tetrandrine is not affected by incubation with actinomycin D, 100 mM KCl, the Cai chelator, 1,2-bi s o-amino-5-fluorophenoxy ethane-N,N,N-,N-,-tetraacetic acid tetraacetoxymethylester BAPTA-AM or in the absence of extracellular Ca. In contrast, stimulation by thapsigargin is inhibited by incubation with actinomycin D, 100 mM KCl, BAPTA-AM or in the absence of extracellular Ca.

ConclusionBoth tetrandrine and thapsigargin stimulate arachidonic acid release, but based on the different results obtained in the presence of actinomycin D, the Cai chelator, 100 mM KCl and in the absence of extracellular Ca, the mechanisms leading to this release and pathways leading to apoptosis and-or cancer chemoprevention may be different. Stimulations by tetrandrine may be mediated by activation of a secretory phospholipase A2, whereas thapsigargin-s stimulations may be mediated by the cytoplasmic Ca-dependent phospholipase A2.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2210-5-12 contains supplementary material, which is available to authorized users.

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Author: Lawrence Levine

Source: https://link.springer.com/







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