Journal Article

Diallyl disulfide inhibits p34<sup>cdc2</sup> kinase activity through changes in complex formation and phosphorylation

Lyn M. Knowles and John A. Milner

in Carcinogenesis

Volume 21, issue 6, pages 1129-1134
Published in print June 2000 | ISSN: 0143-3334
Published online June 2000 | e-ISSN: 1460-2180 | DOI:
Diallyl disulfide inhibits p34cdc2 kinase activity through changes in complex formation and phosphorylation

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Previous studies from our laboratory demonstrated that diallyl disulfide (DADS), an oil-soluble allyl sulfur compound found in processed garlic, markedly suppressed p34cdc2 kinase activity and induced a G2/M phase arrest in cultured human colon tumor (HCT-15) cells. The present studies reveal that suppression of p34cdc2 kinase activity by DADS does not result from direct interactions with the protein, but through changes in factors influencing the formation and conversion of the enzyme to its active form. Flow cytometric analyses showed that the increased proportion of cells in the G2/M phase following DADS treatment was accompanied by an increase in cyclin B1 protein expression. A temporal and dose-dependent response in cyclin B1 expression was observed in cells treated with DADS. Western blot analysis revealed that 50 μM DADS did not influence the quantity of p34cdc2 protein expressed, but did decrease the amount associated with cyclin B1 by 26% (P < 0.05). Exposure of unsynchronized cells to 25 or 50 μM DADS caused a trend towards increased p34cdc2 hyperphosphorylation (17 and 22%, respectively). Exposure of synchronized cells to 100 μM DADS increased p34cdc2 hyperphosphorylation by 15% (P < 0.05). Consistent with its ability to slightly increase the quantity of hyperphosphorylated p34cdc2, DADS, 25 or 50 μM, decreased cdc25C protein expression by 23 and 46%, respectively (P < 0.05). The present studies suggest that the ability of DADS to inhibit p34cdc2 kinase activation occurs because of decreased p34cdc2/cyclin B1 complex formation and modest p34cdc2 hyperphosphorylation.

Keywords: DADS, diallyl disulfide.

Journal Article.  4867 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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