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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
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Article

Selected isothiocyanates rapidly induce growth inhibition of cancer cells

Yuesheng Zhang, Li Tang and Veronica Gonzalez
Yuesheng Zhang
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Li Tang
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Veronica Gonzalez
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DOI:  Published October 2003
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Abstract

Many plant-derived isothiocyanates (ITCs), which occur in human diet, are potent cancer chemopreventive agents in animals. Among the anticarcinogenic mechanisms that have been revealed for ITCs is the inhibition of cell proliferation. We report that exposure of cancer cells to either allyl-ITC (AITC), benzyl-ITC (BITC), or phenethyl-ITC (PEITC) for only 3 h was long enough for the inhibition of cell growth, based on a comparison of IC50 values; regardless of the origin of cancer cells; and even in drug-resistant cells that overexpressed multidrug resistance associated protein-1 (MRP-1) or P-glycoprotein-1 (Pgp-1). In contrast, the inhibitory effect of another ITC, sulforaphane (SF), on these cells was highly time dependent. The finding that some ITCs could inhibit the proliferation of cancer cells in a largely time-independent manner is significant because ITCs that enter the human body are rapidly cleared through urinary excretion. Using human promyelocytic leukemia HL60/S as model cells, and focusing on AITC and BITC, we found that these ITCs modulated multiple cellular targets involved in proliferation, including the disruption of mitochondrial membrane potential, activation of multiple caspases, arrest of cell cycle progression, and induction of differentiation. Again, only a 3-h incubation of the cells with the ITCs was enough to exert their full effect on these targets. Taken together, our findings suggest that selected ITCs can rapidly initiate growth inhibition of cancer cells by simultaneously modulating multiple cellular targets, and their antiproliferative activity may be largely unaffected by their metabolism and disposition in vivo.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Grant Support:NIH Grant RO1 CA80962.

    • Accepted July 15, 2003.
    • Received May 7, 2003.
    • Revision received July 10, 2003.
  • American Association for Cancer Research
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Molecular Cancer Therapeutics: 2 (10)
October 2003
Volume 2, Issue 10
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Selected isothiocyanates rapidly induce growth inhibition of cancer cells
Yuesheng Zhang, Li Tang and Veronica Gonzalez
Mol Cancer Ther October 1 2003 (2) (10) 1045-1052;

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Selected isothiocyanates rapidly induce growth inhibition of cancer cells
Yuesheng Zhang, Li Tang and Veronica Gonzalez
Mol Cancer Ther October 1 2003 (2) (10) 1045-1052;
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Molecular Cancer Therapeutics
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