Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential depolarization in HL-60 and multidrug-resistant cell lines

Jakubikova, Jana, Bao, Yongping ORCID: https://orcid.org/0000-0002-6425-0370 and Sedlák, Jan (2005) Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential depolarization in HL-60 and multidrug-resistant cell lines. Anticancer Research, 25 (5). pp. 3375-3386. ISSN 1791-7530

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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 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.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	https://ar.iiarjournals.org/content/25/5...
Depositing User:	EPrints Services
Date Deposited:	25 Nov 2010 11:10
Last Modified:	13 Nov 2023 16:52
URI:	https://ueaeprints.uea.ac.uk/id/eprint/12964
DOI:

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