Production of the monoterpene limonene and modulation of apoptosis-related proteins in embryonic-mouse NIH 3T3 fibroblast cells by introduction of the limonene synthase gene isolated from Japanese catnip (Schizonepeta tenuifolia).
The monoterpene D-limonene shows cancer preventative and cancer therapeutic activities in vitro and in vivo. Unlike plants, animals are unable to synthesize limonene de novo and obtain limonene through dietary sources. In the present study we established transgenic mouse embryonic NIH 3T3 fibroblast cells that produce limonene by introducing the D-limonene synthase gene obtained from Japanese catnip (Schizonepeta tenuifolia). Apoptosis was not observed in the limonene-producing cells. A concomitant increase in the level of apoptosis-related protein Bcl-2 (B-cell lymphoma protein 2) and decreases in the levels of Bad (Bcl-2 antagonist of cell death) and phosphorylated JNK (c-Jun N-terminal kinase) were observed in limonene-producing cells. Limonene-producing cells may provide a useful new system to investigate the in vivo function of this monoterpene.
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan. ysatomi@koto.kpu-m.ac.jp
Yoshiko
Y
Satomi
Kazuaki
K
Ohara
Kazufumi
K
Yazaki
Michiho
M
Ito
Gisho
G
Honda
Hoyoku
H
Nishino
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D003001:Cloning, Molecular; D053138:Cyclohexenes / Q000378:metabolism*; D005434:Flow Cytometry; D008401:Gas Chromatography-Mass Spectrometry; D019753:Intramolecular Lyases / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D019686:Lamiaceae / Q000201:enzymology*; D000077222:Limonene; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D010957:Plasmids; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013729:Terpenes / Q000378:metabolism*; D014162:Transfection; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494820:Bad protein, mouse; D053138:Cyclohexenes; D019253:Proto-Oncogene Proteins c-bcl-2; D013729:Terpenes; D051025:bcl-Associated Death Protein; D000077222:Limonene; D048031:JNK Mitogen-Activated Protein Kinases; D019753:Intramolecular Lyases; C040265:pinene cyclase I