Antiproliferative/cytotoxic activity of molecular iodine and iodolactones in various human carcinoma cell lines. No interfering with EGF-signaling, but evidence for apoptosis.
Twelve human cancer cell lines and one non-malignant cell line were investigated with respect to a potential antiproliferative/cytotoxic activity of molecular iodine and iodolactones. Except CCL221 colon carcinoma cells, the growth of all cancer cell lines decreased if the cells were cultured in the presence of 10 microM molecular iodine (I(2)) for at least two days. delta-iodolactone (IL, 5 microM) was found to have a similar effect. SH-SY5Y neuroblastoma cells turned out to be most susceptible to both iodine compounds (total inhibition), followed by MCF-7 mammary carcinoma cells (60% and 77.7% inhibition in the presence of I(2) respect. IL) and HS24 lung carcinoma cells (36.3% respect. 40.3% inhibition). In contrast, MCF-10 normal mammary epithelial cells were much less affected by the iodine treatment. In both, SH-SY5Y and MCF-7 cells, I(2) and IL also abolished EGF-induced promotion of cell growth completely. This effect was, however, not due to an interfering with EGF-signaling, because I(2) and IL did not affect the phosphorylation of EGF-receptors, EGF-induced activation of MAP-kinase (Erk(1/2)), or EGF-induced lamellar actin protrusion. A disruption by molecular iodine of mitochondrial transmembrane electrical potential, which was prevented by a pre-treatment of the cells with N-acetyl-cysteine, supports a mitochondria-mediated apoptotic mechanism.
Institut für Zoologie, Universität Hohenheim-Stuttgart, Stuttgart, Germany. roesnerh@uni-hohenheim.de
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001095:Arachidonic Acids / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D007455:Iodine / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism
C026915:6-iodo-5-hydroxy-eicosatrienoic acid, delta-lactone; D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D003603:Cytotoxins; D007783:Lactones; D004815:Epidermal Growth Factor; D007455:Iodine; D020928:Mitogen-Activated Protein Kinases