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Graduate Program in Nutrition and the Nutrition Department, The Pennsylvania State University, University Park, PA 16802
3To whom correspondence should be addressed. E-mail: milnerj{at}mail.nih.gov.
Diallyl disulfide (DADS), a compound found in processed garlic, has been shown to arrest unsynchronized human colon tumor cells (HCT-15) in the G2/M phase of the cell cycle. The present studies were designed to examine whether this cell cycle block related to alterations in protein kinase C (PKC), Ca2+/calmodulin-dependent protein kinase II (CAMK II) or extracellular signal-regulated kinase (ERK) activity. Exposing double thymidine synchronized HCT-15 cells to DADS (25, 50 and 100 µmol/L) for 4 h increased the G2/M population by 30, 31 and 63%, respectively, compared with controls (P < 0.05). PKC and CAM KII activities were not influenced by increasing DADS exposure and thus did not correlate with the block of cells in the G2/M phase. Although ERK activity increased by 44 and 60% after treatment with 100 and 500 µmol/L DADS (P < 0.05), it was not influenced by exposure to 25 or 50 µmol/L DADS. Western blot analysis revealed that although DADS (25, 50, 100 and 500 µmol/L) did not influence the quantity of ERK protein expressed, it did increase its phosphorylation by 39, 52, 73 and 61%, respectively, compared with controls (P < 0.05). These studies provide evidence that early alterations in ERK pathway signaling may contribute to the G2/M arrest observed after DADS exposure. Preliminary data generated using the Clonetech Atlas Human Cancer cDNA Expression Array suggest that alterations in cell cycle, DNA repair and cellular adhesion factors accompany DADS exposure and may also be involved in mediating the block in G2/M progression.
KEY WORDS: • diallyl disulfide • tumor proliferation • G2/M phase • protein kinase • cDNA array
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