Differential effects of antioxidants on the in vitro invasion, growth and lung metastasis of murine colon cancer cells.
We conducted a comparative study of 20 antioxidants including antioxidative vitamins and polyphenols to examine their inhibitory activities against the in vitro invasion, growth and experimental lung metastasis of murine colon 26-L5 carcinoma cells. Among the compounds tested, epigallocatechin gallate (EGCG), gallocatechin gallate and genistein exhibited significant reductions at 77%, 46% and 44% in tumor metastasis by an intraperitoneal administration for 5 d beginning at 3 d before tumor inoculation, respectively. Quercetin also showed a slight but not statistically significant inhibition. Alpha-tocopherol, beta-carotene, ascorbic acid and 2 EGCG-related compounds of epicatechin gallate and epigallocatechin had no effect. EGCG also inhibited tumor metastasis dose-dependently with 98% suppression at 2 micromol; and an almost equivalent inhibition was also produced by only pre-administration of EGCG at the same dose before tumor inoculation. EGCG significantly inhibited tumor cell invasion and proliferation, but its inhibition of these activities was much less effective than that of other compounds which did not show any antimetastatic effect. No statistically significant relationship was observed between the radical scavenging activities of the test compounds and their rates of inhibition of tumor metastasis. The antimetastatic mechanism of EGCG thus seems to be independent of its inhibition of tumor invasion and growth, as well as its radical scavenging activity. Our results suggest that EGCG is potentially beneficial for tumor metastasis inhibition.
Ogasawara
Masaru
M
Toyama Prefectural Institute for Pharmaceutical Research, Imizu, Japan. masaru.ogasawara@pref.toyama.lg.jp
Matsunaga
Takayuki
T
Suzuki
Hideyo
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D013997:Time Factors
D000975:Antioxidants; D016166:Free Radical Scavengers