Dehydrozingerone, a Structural
Analogue of Curcumin, Induces Cell-Cycle Arrest at the G2/M Phase
and Accumulates Intracellular ROS in HT-29 Human Colon Cancer Cells
Dehydrozingerone (1) is a pungent constituent
present in the rhizomes of ginger (Zingiber officinale) and belongs structurally to the vanillyl ketone class. It is a
representative of half the chemical structure of curcumin (2), which is an antioxidative yellow pigment obtained from the rhizomes
of turmeric (Curcuma longa). Numerous studies have
suggested that 2 is a promising phytochemical for the
inhibition of malignant tumors, including colon cancer. On the other
hand, there have been few studies on the potential antineoplastic
properties of 1, and its mode of action based on a molecular
mechanism is little known. Therefore, the antiproliferative effects
of 1 were evaluated against HT-29 human colon cancer
cells, and it was found that 1 dose-dependently inhibited
growth at the G2/M phase with up-regulation of p21. Dehydrozingerone
additionally led to the accumulation of intracellular ROS, although
most radical scavengers could not clearly repress the cell-cycle arrest
at the G2/M phase. Furthermore, two synthetic isomers of 1 (iso-dehydrozingerone, 3, and ortho-dehydrozingerone, 4) were also examined. On comparing
of their activities, accumulation of intracellular ROS was found to
be interrelated with growth-inhibitory effects. These results suggest
that analogues of 1 may be potential chemotherapeutic
agents for colon cancer.