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

Abstract

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.

Gelam Honey and Ginger Potentiate the Anti Cancer Effect of 5-FU against HCT 116 Colorectal Cancer Cells

“…It is quite interesting to note that the same dose of ginger extract is required for inducing highest apoptotic activity in the cancer cells ( Figures 1A and 3B), This could suggest that 3mg/ml is a very effective dose of ginger extract for optimized anti-cancer effect on colon adenocarcinoma. Other studies have also reported the anti proliferative property of ginger extract in colon cancer cells lines HCT 15 and HT 29 (Kim et al, 2008;Lee et al, 2008;Yogosawa et al, 2012). We have previously demonstrated that ginger extract inhibited the growth of HepG2 hepatoma cells and the formation of tumor in liver cancer-induced rats (Mohd Yusof et al, 2008).…”

The role and place of medicinal plants in the strategies for disease prevention

“…Structurally, it is representative of half the chemical structure of curcumin which is a promising phytochemical for the inhibition of malignant tumours, including colon cancer. Yogosawa et al (2012) evaluated the antiproliferative effects of dehydrozingerone against HT-29 human colon cancer cells, and it was found that it 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.…”

Reactive Oxygen Species and Colorectal Cancer

“…However, other antioxidants did not reverse the effects of dehydrozingerone on cell cycle arrest. The authors indicate that further studies are required to confirm the involvement of ROS, since dehydrozingerone is structurally similar to curcumin and could conjugate with glutathione, the direct metabolite of N-acetyl-L-cysteine to reduce its potency in the cell [29]. A study on the anticancer effects of curcuminoids in both HT-29 and SW480 colon cancer cells and CCD-18Co colon fibroblasts reported inhibition of HT-29 and SW480 colon cancer cell growth and enhanced activity of the chemotherapeutic agent 5-fluorouracil.…”