Inhibitory effects of active substances isolated from Cassia garrettiana heartwood on tumor growth and lung metastasis in Lewis lung carcinoma-bearing mice (Part 1).
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. We isolated the two active substances from the methanol extract of C. garrettiana: compound 1 was identified as Cassigarol A and the determination of the structure of compound 2 is now in progress. We examined the effect of the active substance (compound 1, Cassigarol A) on tumor growth and lung metastasis in LLC-bearing and primary tumor-removed mice and found that Cassigarol A (50 mg and 100 mg/kg x 2/day) inhibited the tumor growth and metastasis to the lung. In addition, Cassigarol A inhibited the plasmin activity and the formation of capillary-like networks of human umbilical vein endothelial cells (HUVECs) at concentrations of 10 to 100 microM. Therefore, it is suggested that the antitumor and antimetastatic activities of Cassigarol A might be due to the inhibition of plasmin activity and formation of tubes (angiogenesis) from HUVECs.
Kimura
Y
Y
Second Department of Medical Biochemistry, School of Medicine, Ehime University, Japan. yokim@m.ehime-u.acjp
Baba
K
K
Okuda
H
H
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D002366:Cassia; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology / Q000517:prevention & control / Q000556:secondary* / Q000601:surgery; D000432:Methanol; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009362:Neoplasm Metastasis; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000627:therapeutic use*; D010936:Plant Extracts / Q000627:therapeutic use; D010946:Plants, Medicinal; D013154:Spleen / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects; D013997:Time Factors
D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D010636:Phenols; D010936:Plant Extracts; C075680:cassigarol A; D005341:Fibrinolysin; D000432:Methanol