Inhibitory effects of active substances isolated from Cassia garrettiana heartwood on tumor growth and lung metastasis in Lewis lung carcinoma-bearing mice (Part 2).
Previously, we reported that a methanol extract (500 mg/kg x 2/day) of the heartwood of Cassia garrettiana inhibited the tumor growth and metastasis to the lung in Lewis lung carcinoma (LLC)-bearing mice. Furthermore, we isolated the two active substances from the methanol extract of C. garrettiana and identified compound 1 as cassigarol A. In the present study, compound 2 was identified as 3, 3', 4, 5'-tetrahydroxy stilbene (piceatannol) based on the 1H-NMR spectral data and products formed by oxidation with potassium permanganate. We examined the active substance (compound 2, piceatannol) and its acetylated derivative on the tumor growth and lung metastasis in LLC-bearing and carcinectomized mice. Piceatannol (50 mg and 100 mg/kg x 2/day) did not affect the tumor growth, while piceatannol acetate (50 mg and 100 mg/kg x 2/day) significantly inhibited the tumor growth. Piceatannol and its derivative piceatannol acetate inhibited the metastasis to the lung dose-dependently in carcinectomized mice. Moreover, piceatannol and piceatannol acetate prolonged the survival time and increased the survival rate in carcinectomized mice. In addition, piceatannol inhibited the formation of capillary-like networks of human umbilical vein endothelial cells (HUVECs) at the concentrations of 10 to 100 microM, but its acetylated derivative did not. Therefore, it is suggested that the antimetastatic activities of piceatannol might be due to the inhibition of tube formation (angiogenesis) of HUVECs.
Kimura
Y
Y
Second Department of Medical Biochemistry, School of Medicine, Ehime University, Japan. yokim@m.ehime-u.ac.jp
Baba
K
K
Okuda
H
H
D000107:Acetylation; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000503:physiopathology; D002366:Cassia; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009362:Neoplasm Metastasis; D010936:Plant Extracts; D010946:Plants, Medicinal; D013267:Stilbenes / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010936:Plant Extracts; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene