Carcinogenesis Advance Access published online on July 4, 2003
Carcinogenesis, doi:10.1093/carcin/bgg105
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Gifu International Institute of Biotechnology, Mitake, Kani-gun, Gifu 505-0116, Japan; Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-5858, Japan; Gifu Prefectural Institute of Health and Environmental Sciences, Kakamigahara, Gifu 504-0838, Japan
* Corresponding author. E-mail: yakao{at}giib.or.jp.
Received 8 July 2002
; revised 25 March 2003
; accepted 12 June 2003
Twenty resveratrol (3,5,4'-trihydroxystilbene) derivatives, which were isolated from stem bark of Vatica rassak (Dipterocarpaceae), were evaluated for in vitro cytotoxicity against a panel of human tumor cell lines. Among them, 7 compounds displayed marked cytotoxicity. Vaticanol C as a major component induced a considerable cytotoxicity in all cell lines tested and exhibited growth suppression in colon cancer cell lines at low dose. Vaticanol C caused two cell lines (SW480 and HL60) to induce cell death at 4-7 times lower concentrations, compared to resveratrol. The growth suppression by vaticanol C was found to be due to apoptosis which was assessed by morphological findings (nuclear condensation and fragmentation) and DNA ladder formation in the colon cancer cell lines. The apoptosis in SW480 colon cancer cells was executed by the activation of caspase-3, which was shown by Western blot and apoptosis inhibition assay. Furthermore, the mitochondrial membrane potential of apoptotic SW480 cells after 12 h treatment with vaticanol C was significantly lost, and concurrently the cytochrome c release and activation of caspase-9 were also detected by Western blot analysis. Overexpression of Bcl-2 protein in SW480 cells significantly prevented the cell death induced by vaticanol C. Taken together, the findings presented here indicate that vaticanol C induced marked apoptosis in malignant cells mainly by affecting mitochondrial membrane potential.
Vaticanol C, stilbene tetramer, apoptosis, mitochondria, cancer cells
Anti-tumor effect of resveratrol oligomers against human cancer cell lines and the molecular mechanism of apoptosis induced by vaticanol C
2 Gifu International Institute of Biotechnology, Mitake, Kani-gun, Gifu 505-0116, Japan
3 Gifu Prefectural Institute of Health and Environmental Sciences, Kakamigahara, Gifu 504-0838, Japan
4 Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-5858, Japan; Gifu Prefectural Institute of Health and Environmental Sciences, Kakamigahara, Gifu 504-0838, Japan
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