Antitumor effect of the cinnamaldehyde derivative CB403 through the arrest of cell cycle progression in the G2/M phase.
Cinnamaldehydes have been shown to have inhibitory effects on farnesyl protein transferase (FPTase; EC 2.5.1.29) in vitro, angiogenesis, cell-cell adhesion, and tumor cell growth and to be immunomodulators. However, the mechanisms responsible for these effects remain unknown. To elucidate the molecular mechanism of the cinnamaldehyde derivative CB403 for growth inhibition, CB403 was synthesized from 2'-hydroxycinnamaldehyde. CB403-treated cells were weakly adherent to the culture dishes. In addition, CB403 inhibited tumor growth in these cells in a concentration-dependent manner. FACS analysis using human cancer cells treated with this compound showed cell cycle arrest in mitosis, which was correlated with a marked increase in the amount of cyclin B1. Furthermore, CB403 blocked in vivo growth of human colon and breast tumor xenografts without loss of body weight in nude mice. These results support the hypothesis that the cinnamaldehyde derivative CB403 exerts cytostatic properties by inducing mitotic arrest in cancer cells.
Jeong
Ha-Won
HW
Korea Research Institute of Bioscience and Biotechnology, 52 Uendong Yoosunggu, Taejeon 305-600, South Korea.
Han
Dong Cho
DC
Son
Kwang-Hee
KH
Han
Mi Young
MY
Lim
Jong-Seok
JS
Ha
Ji-Hong
JH
Lee
Chang Woo
CW
Kim
Hwan Mook
HM
Kim
Hyoung-Chin
HC
Kwon
Byoung-Mog
BM
D000171:Acrolein / Q000031:analogs & derivatives* / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000187:drug effects; D010647:Phenyl Ethers / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C474928:CB 403; D010647:Phenyl Ethers; D000171:Acrolein; C012843:cinnamaldehyde