2'-Benzoyloxycinnamaldehyde inhibits tumor growth in H-ras12V transgenic mice via downregulation of metallothionein.
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.
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Heun-Sik
HS
Lee
So Young
SY
Lee
Hye-Lin
HL
Ha
Dong Cho
DC
Han
Jong-Min
JM
Han
Tae-Sook
TS
Jeong
Dae-Yeul
DY
Yu
Young-Il
YI
Yeom
Byoung-Mog
BM
Kwon
Eun-Yi
EY
Moon
D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D001565:Benzoates / Q000008:administration & dosage* / Q000302:isolation & purification; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D035261:Plant Components, Aerial / Q000737:chemistry; D019664:Polygonaceae / Q000737:chemistry; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D047368:Tumor Burden; D018631:ras Proteins / Q000235:genetics
C484327:2'-benzoyloxycinnamaldehyde; D000970:Antineoplastic Agents; D001565:Benzoates; D020033:Protein Isoforms; D012333:RNA, Messenger; D000171:Acrolein; D008668:Metallothionein; D018631:ras Proteins