Efficient induction of chromosome-type aberrations by topoisomerase II inhibitors closely associated with stabilization of the cleavable complex in cultured fibroblastic cells

Suzuki, Hiroshi; Ikeda, Tomotake; Yamagishi, Takehiro; Nakaike, Shiro; Nakane, Sadao; Ohsawa, Motoyasu

doi:10.1016/0027-5107(95)00005-4

Cited by 28 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of GCP activity is not fully elucidated, and is probably attributable to multiple cytotoxic and kinase inhibitory effects. Genistein is a topoisomerase II inhibitor that stimulates double‐strand DNA breaks [48,49]. We have previously shown that GCP can moderately suppress phosphorylation of AKT and mTOR‐p70S6K signalling, while elevating levels of p53 [12].…”

Section: Discussionmentioning

confidence: 99%

Genistein combined polysaccharide enhances activity of docetaxel, bicalutamide and Src kinase inhibition in androgen‐dependent and independent prostate cancer cell lines

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE To determine the benefit of genistein combined polysaccharide (GCP) in combination with the androgen receptor antagonist bicalutamide, the antimicrotubule taxane docetaxel, and the Src kinase inhibitor pp2 as part of a treatment regimen for advanced prostate cancer (CaP). MATERIALS AND METHODS The growth inhibitory and apoptotic effects of GCP in combination with bicalutamide, docetaxel and pp2 were evaluated in both the androgen‐dependent LNCaP line, and three androgen‐independent lines: CWR22Rv1, PC‐3, and LNCaP‐R273H. The LNCaP‐R273H model is an LNCaP variant expressing a p53GOF allele; like CWR22Rv1 and PC‐3, it is able to grow in a minimal androgen environment. The effects of GCP treatment in combination with the aforementioned drugs were measured using an MTT assay, Western blotting, flow cytometric analysis, and caspase activation assay. Altered schedules of drug administration were explored using combinations of GCP and docetaxel. RESULTS GCP potentiated the activity of docetaxel in all four cell lines, resulting in growth inhibition and increased apoptosis. The combination of GCP and bicalutamide had enhanced activity in both the LNCaP and LNCaP‐R273H lines, which may better represent patient tumour cells after progression to androgen independence. Administration of docetaxel followed by GCP resulted in a synergistic interaction in LNCaP cells, with increased apoptosis. By contrast, GCP administered first showed subadditivity, probably resulting from GCP‐mediated induction of G1 arrest interfering with docetaxel activity. CONCLUSION These data suggest that GCP, an isoflavone‐enriched compound with minimal side‐effects and far superior intestinal absorption rate of genistein, has significant clinical potential in combination with docetaxel, bicalutamide or targeted agents for the treatment of advanced CaP.

show abstract

Section: Discussionmentioning

confidence: 99%

Genistein combined polysaccharide enhances activity of docetaxel, bicalutamide and Src kinase inhibition in androgen‐dependent and independent prostate cancer cell lines

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This drug was not mutagenic in Salmonella typhimurium and V79 Chinese hamster cells [Westendorf et al, 1984], and induced only chromatid-type aberrations in both in vitro [Suzuki and Nakane, 1994;Suzuki et al, 1995] and in vivo test systems [Nersessian et al, 1991].…”

Section: Topoisomerase II Catalytic Inhibitormentioning

confidence: 99%

Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test

Lehmann

Vilar

Franco

et al. 2004

Environ and Mol Mutagen

View full text Add to dashboard Cite

Anthracyclines have been widely used as anticancer drugs against different types of human cancers. The present study evaluated the mutagenic and recombinagenic properties of two anthracycline topoisomerase II (topo II) poisons, daunorubicin (DNR) and idarubicin (IDA), as well as the related topo II catalytic inhibitor aclarubicin (ACLA), using the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. The three anthracyclines were positive in this bioassay, producing mainly mitotic homologous recombination. The results for spot-size distribution and recombinagenic activity indicate that recombinational DNA damage accounts for approximately 91, 86, and 62% of DNR, IDA, and ACLA genotoxicity, respectively. Besides being a catalytic inhibitor of topo II, ACLA is also a topoisomerase I (topo I) poison. This dual topo I and II inhibitory effect, associated with its DNA-intercalating activity, could contribute to the activity of ACLA in the SMART assay.

show abstract

“…In agreement with all these observations, the cytotoxic and genotoxic effects of these b-carboline alkaloids have been related to their injurious action on DNA (Sasaki et al 1992;Shimoi et al 1992;Meester 1995;Picada et al 1997) because of the intercalation of DNA (Meester 1995;Taira et al 1997;Balon et al 1999). Intercalating agents such as acridine and quinacrine stains, as well as antineoplastic agents, can induce chromosome aberrations and DNA strand breaks in mammalian cells (De Marini & Laurence 1992;Suzuki et al 1995;Araú jo et al 1998;Palitti 1998). Moreover, many intercalating agents are DNA topoisomerase inhibitors and can interfere with the breakage-rejoining action of these enzymes, resulting in the formation of complexes between enzyme and DNA, favoring DNA strand breaks (Chen & Liu 1994;Wang 1996Wang & 1998Hammonds et al 2000).…”

Section: Discussionmentioning

confidence: 76%

Genotoxic Effects of the Alkaloids Harman and Harmine Assessed by Comet Assay and Chromosome Aberration Test in Mammalian Cells in vitro

Boeira

Silva

Erdtmann

et al. 2001

Pharmacology & Toxicology

View full text Add to dashboard Cite

Harman and harmine are b-carboline alkaloids which are present in plants widely used in medical practice, in beverages used for religious purposes in Brazil, as well as in tobacco smoke and over cooked food. In view of the controversial results observed in the literature about the mutagenic effects of these alkaloids, we studied their cytotoxic and genotoxic effects in V79 Chinese hamster lung fibroblasts in vitro using single-cell gel assay, Comet assay, either in the presence or in absence of an exogenous metabolic activation system (S9-mix), and by the chromosome aberration test without S9-mix. Harmine was more cytotoxic than harman. Both harman and harmine increased aberrant cell frequency and induced DNA damage by the Comet assay. These results suggest that harman and harmine are genotoxic in V79 cells, probably as a consequence of their ability to induce DNA strand breaks.

show abstract

Efficient induction of chromosome-type aberrations by topoisomerase II inhibitors closely associated with stabilization of the cleavable complex in cultured fibroblastic cells

Cited by 28 publications

References 29 publications

Genistein combined polysaccharide enhances activity of docetaxel, bicalutamide and Src kinase inhibition in androgen‐dependent and independent prostate cancer cell lines

Genistein combined polysaccharide enhances activity of docetaxel, bicalutamide and Src kinase inhibition in androgen‐dependent and independent prostate cancer cell lines

Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test

Genotoxic Effects of the Alkaloids Harman and Harmine Assessed by Comet Assay and Chromosome Aberration Test in Mammalian Cells in vitro

Contact Info

Product

Resources

About