Unbound MEDLINE

Enhancement of cisplatin cytotoxicity by benzyl isothiocyanate in HL-60 cells.

Abstract

Cis-diamminedichloroplatinum (II) (cisplatin) is one of the most widely used chemotherapeutic drugs, but its effectiveness is limited by tumor cell resistance and the severe side effects it causes. One strategy for overcoming this problem is the concomitant use of natural dietary compounds as therapeutic agents. Benzyl isothiocyanate (BITC) is a promising chemopreventive agent found in cruciferous vegetables and papaya fruits. The aim of this study was to investigate the effects of BITC on cisplatin-induced cytotoxicity in human promyelocytic leukemia cells and normal human lymphocytes. The combined treatment of HL-60 cells with BITC followed by cisplatin (BITC/cisplatin) caused a significant decrease in cell viability. BITC also increased apoptotic cell death compared to cisplatin treatment alone. In normal human lymphocytes, BITC did not enhance the cytotoxic effects of cisplatin. Cellular exposure to BITC/cisplatin increased reactive oxygen species (ROS) generation but decreased the total glutathione (GSH) level in HL-60 cells. Pretreatment of HL-60 cells with N-acetylcysteine or glutathione monoethyl ester effectively decreased BITC/cisplatin-induced cell death. The addition of the extracellular signal-regulated kinase (ERK) inhibitor PD98059 abolished BITC/cisplatin-induced apoptosis. Taken together, our results suggest that BITC enhances cisplatin-induced cytotoxicity through the generation of ROS, depletion of GSH, and ERK signaling in HL-60 cells.

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  • Publisher Full Text
  • Authors

    Lee Y, Kim YJ, Choi YJ, Lee JW, Lee S, Chung HW

    Institution

    School of Public Health and Institute of Health and Environment, Seoul National University, 1 Gwanka-ro, Gwankak-gu, Seoul 151-742, Republic of Korea.

    Source

    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 50:7 2012 Jul pg 2397-406

    MeSH

    Antineoplastic Agents
    Base Sequence
    Cisplatin
    DNA Primers
    Drug Synergism
    HL-60 Cells
    Humans
    Isothiocyanates
    Real-Time Polymerase Chain Reaction

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22525867