Inhibition by evodiamine of hepatocyte growth factor-induced invasion and migration of tumor cells.
Tumor cell motility plays a crucial role in the establishment of tumor metastasis and is affected by a variety of host-derived factors during the event. Hepatocyte growth factor (HGF) is one of these factors and stimulates tumor cell migration remarkably. We previously reported that evodiamine has a marked inhibitory activity on tumor cell invasion and migration in vitro. In this study, the effects of evodiamine on HGF-induced invasion and migration of tumor cell lines, colon 26-L5 carcinoma, B16-F10 melanoma and Lewis lung carcinoma (LLC) were examined. HGF promoted invasive activity of tumor cell lines with maximal induction of 1.8 times at 30 ng/ml for colon 26-L5 and LLC cells, and 2.0 times at 10 ng/ml for B16-F10 cells. Evodiamine inhibited the HGF-stimulated tumor cell invasion and migration in a concentration-dependent manner, and achieved complete suppression at 30 microM in all of the cell lines tested. When tumor cells were seeded on fibronectin-coated plates with evodiamine, their spreading on the plate was obviously inhibited, while their adhesiveness to fibronectin was unaffected. Evodiamine showed a marginal effect on tumor cell growth in a 24-h incubation, although it exhibited a marked inhibition in an over 48-h incubation. These results suggest that evodiamine suppressed HGF-stimulated invasion and migration of tumor cells partly through inhibition of cell spreading.
Ogasawara
Masaru
M
Toyama Prefectural Institute for Pharmaceutical Research, 17-1 Nakataikouyama, Kosugi-machi, Imizu-gun, Toyama 939-0363, Japan. masaru.ogasawara@pref.toyama.lg.jp
Suzuki
Hideyo
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms; D032086:Evodia / Q000737:chemistry; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D008546:Melanoma, Experimental; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011799:Quinazolines; D017228:Hepatocyte Growth Factor; C049639:evodiamine