Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance.
The triterpenoid fraction (100 and 200 mg/kg) of the fruit bodies of Ganoderma lucidum inhibited primary solid-tumor growth in the spleen, liver metastasis and secondary metastatic tumor growth in the liver in intrasplenic Lewis lung carcinoma (LLC)-implanted mice. In addition, the triterpenoid fraction (800 micrograms/mL) inhibited angiogenesis induced by Matrigel (a soluble basement membrane extract of the Engelbreth-Holm-Swam (EHS) tumor) supplemented with vascular endothelial growth factor (VEGF) and heparin in an in vivo model. This suggested that the antitumor and antimetastatic activities of the triterpenoid fraction of G. lucidum might be due to the inhibition of tumor-induced angiogenesis. Next, we attempted to isolate the active substance(s) using the in vivo assay system of Matrigel-induced angiogenesis. The acidic fraction of the triterpenoid fraction inhibited the Matrigel-induced angiogenesis. Compound I was isolated from the acidic fraction as an active substance that inhibited the Martigel-induced angiogenesis. Compound I was identified as ganoderic acid F based on the data of IR, 1H- and 13C-NMR and MS analyses.
Kimura
Yoshiyuki
Y
Second Department of Medical Biochemistry, School of Medicine, Ehime University, Shigenobu-cho, Onsen-gun, Ehime 791-095, Japan. yokim@m.ehimeu.ac.jp
Taniguchi
Masahiko
M
Baba
Kimiye
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000517:prevention & control / Q000556:secondary; D003094:Collagen; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004338:Drug Combinations; D005260:Female; D032902:Ganoderma / Q000737:chemistry*; D007797:Laminin; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011509:Proteoglycans; D013160:Splenic Neoplasms / Q000188:drug therapy / Q000473:pathology; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D014315:Triterpenes; C059485:matrigel; D003094:Collagen