title: Sulforaphane induces DNA damage and mitotic abnormalities in human osteosarcoma MG-63 cells: correlation with cell cycle arrest and apoptosis.
abstract: Osteosarcoma is a recalcitrant bone malignancy with poor responsiveness to treatments; therefore, new chemotherapeutic compounds are needed. Sulforaphane (SFN) has been considered a promising chemotherapeutic compound for several types of tumors by inducing apoptosis and cytostasis, but its effects (e.g., genotoxicity) in osteosarcoma cells remains exploratory. In this work, the MG-63 osteosarcoma cell line was exposed to SFN up to 20 μM for 24 and 48 h. SFN induced G2/M phase arrest and decreased nuclear division index, associated with disruption of cytoskeletal organization. Noteworthy, SFN induced a transcriptome response supportive of G2/M phase arrest, namely a decrease in Chk1- and Cdc25C-encoding transcripts, and an increase in Cdk1-encoding transcripts. After 48-h exposure, SFN at a dietary concentration (5 μM) contributed to genomic instability in the MG-63 cells as confirmed by increased number of DNA breaks, clastogenicity, and nuclear and mitotic abnormalities. The increased formation of nucleoplasmic bridges, micronuclei, and apoptotic cells positively correlated with loss of viability. These results suggest that genotoxic damage is an important step for SFN-induced cytotoxicity in MG-63 cells. In conclusion, SFN shows potential to induce genotoxic damage at low concentrations and such potential deserves further investigation in other tumor cell types.
authors.affiliation: a CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology , University of Aveiro , Campus Universitário de Santiago , Aveiro , Portugal.
authors.forename: José Miguel P
authors.initials: JM
authors.lastname: Ferreira de Oliveira
authors.forename: Catarina
authors.initials: C
authors.lastname: Remédios
authors.forename: Helena
authors.initials: H
authors.lastname: Oliveira
authors.forename: Pedro
authors.initials: P
authors.lastname: Pinto
authors.forename: Francisco
authors.initials: F
authors.lastname: Pinho
authors.forename: Sónia
authors.initials: S
authors.lastname: Pinho
authors.forename: Maria
authors.initials: M
authors.lastname: Costa
authors.forename: Conceição
authors.initials: C
authors.lastname: Santos
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D003599:Cytoskeleton / Q000737:chemistry; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D012516:Osteosarcoma / Q000378:metabolism; D013454:Sulfoxides
chemical_list: D017879:Isothiocyanates; D013454:Sulfoxides; C016766:sulforaphane