title: Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential depolarization in HL-60 and multidrug-resistant cell lines.
abstract: 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 microM, 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.
authors.affiliation: Nutrition Division, Institute of Food Research, Norwich Research Park, Norwich, NR4 7UA, UK.
authors.forename: Jana
authors.initials: J
authors.lastname: Jakubikova
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bao
authors.forename: Jan
authors.initials: J
authors.lastname: Sedlak
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D017879:Isothiocyanates / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D017879:Isothiocyanates; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014750:Vincristine; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C421109:multidrug resistance-associated protein 1