2′-Benzoyloxycinnamaldehyde Inhibits Tumor Growth in H-ras12V Transgenic Mice via Downregulation of Metallothionein

Abstract

Cinnamaldehydes have been reported to induce apoptosis in human carcinomas through the generation of reactive oxygen species (ROS). 2′-benzoyloxycinnamaldehyde (BCA) has been reported to inhibit tumor formation in H-ras12V transgenic mice. To see the antitumor effects of BCA, BCA was administrated intraperitoneally (50 mg/kg) to H-ras12V transgenic mice for 3 wk, and it was found that the hepatic tumor volume and the total number of tumors were decreased in BCA-treated mice as compared to control H-ras12V transgenic mice. To identify possible target genes responsible for BCA antitumor effects in H-ras12V transgenic mice, cDNA microarray analyses were performed comparing gene expression between BCA treated and control transgenic mice. We found that 42 genes were downregulated, and 40 genes were upregulated in the BCA-treated transgenic mice. The downregulated genes included several genes involved in ROS regulation and immune response (aconitase, metallothionein-1, metallothionein-2, and purine nucleoside phosphorylase). The expression of ROS-related genes, metallothionein 1 and metallothionein 2, was decreased more than twofold with BCA treatment (P < 0.001). It was confirmed by RT-PCR and immunohistochemical analyses. The inhibition of tumor formation and growth in H-ras12V transgenic mice by BCA was mediated through inhibition of the expression of the ROS scavengers metallothionein 1 and metallothionein 2.

ACKNOWLEDGMENTS

This work was supported by the Plant Diversity Research Center of the 21st Century Frontier Research Program, the National Chemical Genomics Research Program, and the Korea Food and Drug for the Standardization of Oriental Herbal Medicines.

Notes

^a Abbreviations are as follows: RT-PCR, Reverse transcriptase polymerase chain reaction; Mt, metallothionein.

^a Abbreviations are as follows: PCR, polymerase chain reaction; MT, metallothionein.

^a Abbreviations are as follows: BCA, 2′-benzoyloxycinnamaldehyde; cDNA, complementary DNA; mRNA, messenger RNA.

^b Numbers represent log₂ ratio of mRNA expression of Tween-80 or BCA treatment in H-ras12V transgenic mice relative to wild type mice.