Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential depolarization in HL-60 and multidrug-resistant cell lines.
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.
Jakubikova
Jana
J
Nutrition Division, Institute of Food Research, Norwich Research Park, Norwich, NR4 7UA, UK.
Bao
Yongping
Y
Sedlak
Jan
J
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
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