title: 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.
authors.affiliation: School of Public Health and Institute of Health and Environment, Seoul National University, 1 Gwanka-ro, Gwankak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Younghyun
authors.initials: Y
authors.lastname: Lee
authors.forename: Yang Jee
authors.initials: YJ
authors.lastname: Kim
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Choi
authors.forename: Joong Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sunyeong
authors.initials: S
authors.lastname: Lee
authors.forename: Hai Won
authors.initials: HW
authors.lastname: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001483:Base Sequence; D002945:Cisplatin / Q000633:toxicity*; D017931:DNA Primers; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D017879:Isothiocyanates / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D017879:Isothiocyanates; C031403:benzyl isothiocyanate; D002945:Cisplatin