Anti-invasive and metastatic activities of evodiamine.
We have recently reported that evodiamine can suppress in vitro invasion and lung metastasis by colon 26-L5 carcinoma cells. To extend our study, we examine here the anti-invasive and metastatic effects of evodiamine on Lewis lung carcinoma (LLC) and B16-F10 melanoma in addition to colon 26-L5 carcinoma. Critical structures of evodiamine for the activities were also evaluated by comparison with compounds possessing structures similar to that of evodiamine. Evodiamine concentration-dependently inhibited the invasion of B16-F10, LLC and colon 26-L5 cells with IC(50) values of 2.4 micro M, 4.8 micro M and 3.7 micro M, respectively. Pre-treatment of colon 26-L5 cells with evodiamine before inoculation into mice caused significant suppression of the liver metastasis as well as the lung metastasis. Lung metastasis by LLC is also inhibited significantly by pre-exposure to evodiamine. When the anti-migratory activity of evodiamine was compared with that of evodiamine-like compounds, rutaecarpine lacking a methyl group at N-14 and a hydrogen at C-13 b exhibited much less effect than evodiamine. In addition, reserpine, having beta-configurated hydrogen at C-13 b, inhibited tumor cell migration more potently than yohimbine, having alpha-configurated hydrogen at the same position. These results suggest that evodiamine may be useful as a leading compound for agents in tumor metastasis therapy. Also, the presence of a methyl group at N-14 and the configuration of hydrogen at C-13 b may be responsible for the inhibitory activities of evodiamine.
Ogasawara
Masaru
M
Toyama Prefectural Institute for Pharmaceutical Research, Toyama, Japan. masaru.ogasawara@pref.toyama.jp
Matsunaga
Takayuki
T
Takahashi
Satoshi
S
Saiki
Ikuo
I
Suzuki
Hideyo
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy; D032086:Evodia / Q000737:chemistry*; D005260:Female; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011799:Quinazolines; C049639:evodiamine