TY - JOUR T1 - Isothiocyanates Induce Cell Cycle Arrest, Apoptosis and Mitochondrial Potential Depolarization in HL-60 and Multidrug-resistant Cell Lines JF - Anticancer Research JO - Anticancer Res SP - 3375 LP - 3386 VL - 25 IS - 5 AU - JANA JAKUBIKOVA AU - YONGPING BAO AU - JAN SEDLAK Y1 - 2005/09/01 UR - http://ar.iiarjournals.org/content/25/5/3375.abstract N2 - Isothiocyanates from cruciferous vegetables have been identified as potent anticancer agents in animal and human epidemiological studies. The present study compared the biological activities of six dietary isothiocyanates (ITCs), allyl-ITC (AITC), benzyl-ITC (BITC), phenethyl-ITC (PEITC), sulforaphane (SFN), erucin (ERN) and iberin (IBN), on cell cycle progression, apoptosis induction and mitochondrial transmembrane potential in multidrug-resistant HL60/ADR (MRP-1-positive) and HL60/VCR (Pgp-1-positive) cells in comparison to the parent cell line HL60. Multidrug-resistant HL60/ADR and HL60/VCR cells were less sensitive than the parental HL60 cells to all the six tested ITCs, since the medians of IC50 values were 2.8- and 2.0-fold higher. All the selected ITCs induced time- and dose-dependant G2/M arrest, with the most effective AITC (10 μM, 24 h) inducing 52% G2/M accumulation in HL60 cells. Apoptosis was determined by Annexin V-FITC staining, metabolic conversion of fluorescein diacetate and sub-G1 population quantification. Cell cycle distribution and mitochondrial JC-1 aggregation were determined by flow cytometry. The effectiveness of ITCs in apoptosis induction and mitochondrial potential dissipation followed the order: BITC=PEITC>ERN=IBN>AITC>SFN. This study demonstrates that dietary ITCs are mitotic inhibitors and/or apoptosis inductors and suggests they could be chemotherapeutic agents in cells with multidrug resistance phenotypes. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -