Inhibition of cell cycle and induction of apoptosis by sulforaphane in cell lines carrying various inherited BRCA1 mutations.
The important aspect of sulforaphane (SFN) chemopreventive activity is its ability to induce cell growth inhibition and apoptosis. In this study, the effect of SFN on lymphoblastoid cells derived from people carrying four different germ-line mutations in BRCA1 gene was tested and compared to the effect of SFN on wild-type cells. The mutations studied were C61G, 3819del5, 4153delA and 5382INSC. Changes in cell viability and density after SFN treatment were evaluated, as well as cell cycle progression, changes in mitochondrial membrane potential, and phosphatidylserine externalization. SFN was shown to reduce cell viability and density in all cell lines tested. Cell cycle block in S-phase and the occurence of simultaneous apoptosis were observed. The concentration of SFN needed to elicit a comparable effect on each cell line was varied. We found that the effect of SFN on cells carrying different inherited mutations depended on mutation type.
Misiewicz
Irena
I
Confocal Microscopy Laboratory, National Institute of Public Health, Chelmska 30/34, 00-725 Warsaw, Poland.
Kozar
Agata
A
Skupinska
Katarzyna
K
Kowalska
Elzbieta
E
Lubinski
Jan
J
Kasprzycka-Guttman
Teresa
T
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D017879:Isothiocyanates; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D008928:Mitochondria / Q000473:pathology; D009154:Mutation; D010718:Phosphatidylserines / Q000737:chemistry; D016196:S Phase; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D013997:Time Factors
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D010718:Phosphatidylserines; D013454:Sulfoxides; D013861:Thiocyanates; D048031:JNK Mitogen-Activated Protein Kinases; C016766:sulforaphane