Depressed p34cdc2 kinase activity and G2/M phase arrest induced by diallyl disulfide in HCT-15 cells

L M Knowles1, J A Milner

  • 1Nutrition Department, Pennsylvania State University, University Park 16802, USA.

Nutrition and Cancer
|June 19, 1998
PubMed

Insights

Diallyl disulfide (DADS) exhibits antiproliferative effects on colon tumor cells by arresting them in the G2/M phase. This cell cycle arrest is linked to the inhibition of p34cdc2 kinase activity.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Colon cancer remains a significant health concern, necessitating research into novel therapeutic agents.
  • Diallyl disulfide (DADS), a compound found in garlic, has shown potential anticancer properties.
  • Understanding the molecular mechanisms underlying DADS's effects is crucial for its therapeutic development.

Purpose of the Study:

  • To investigate the antiproliferative effects of diallyl disulfide (DADS) on human colon tumor cells (HCT-15).
  • To elucidate the cell cycle regulatory mechanisms and kinase activities affected by DADS exposure.
  • To determine the relationship between DADS concentration, duration of exposure, and its impact on cell proliferation.

Main Methods:

  • Cultured human colon tumor cells (HCT-15) were treated with varying concentrations and durations of DADS.
  • Cell cycle distribution was analyzed using flow cytometry to assess phase proportions (G1, G2/M).
  • p34cdc2 kinase activity was measured in DADS-treated cells to evaluate its inhibition.

Main Results:

  • DADS demonstrated significant antiproliferative activity in HCT-15 cells.
  • DADS treatment led to a dose- and time-dependent increase in G2/M phase cell arrest.
  • Exposure to DADS inhibited p34cdc2 kinase activity, with maximum inhibition observed at 25 microM.

Conclusions:

  • Diallyl disulfide (DADS) effectively inhibits colon tumor cell proliferation by inducing G2/M phase arrest.
  • Inhibition of p34cdc2 kinase activity is an early cellular event contributing to DADS's antiproliferative property.
  • Reversibility of proliferation upon DADS removal suggests a manageable therapeutic window.

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