Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice.
We previously reported that gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, can induce apoptosis in four kinds of human lung cancer cell lines in vitro. The present study further investigated the in vivo anti-tumor effects of orally administered gallic acid. Gallic acid reduced cell viability of LL-2 mouse lung cancer cells in vitro dose dependently, with a 50% inhibitory concentration (IC50) value of around 200 microM. C57Black mice were transplanted with LL-2 cells, and administered gallic acid (1 mg/ml in drinking water, ad libitum) and/or cisplatin (4 mg/kg i.p. injection, once a week). The average weight of the transplanted tumors, obtained at 29 days after transplantation, in the mice of control, gallic acid-treated cisplatin-treated and cisplatin plus gallic acid-treated groups was 4.02, 3.65, 3.19 and 1.72 g, respectively. The average tumor weight of the mice treated with cisplatin combined with gallic acid was significantly smaller than that of the control group (p<0.05). The amount of apoptotic cells in the tumor tissues of mice treated with gallic acid and/or cisplatin was significantly higher than those of the control mice. Combination of gallic acid and cisplatin increased the tumor cell apoptosis compared with the treatment with cisplatin alone. The present findings suggest that the combination of gallic acid with an anti-cancer drug, including cisplatin, may be an effective protocol for lung cancer therapy.
Kawada
M
M
Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan.
Ohno
Y
Y
Ri
Y
Y
Ikoma
T
T
Yuugetu
H
H
Asai
T
T
Watanabe
M
M
Yasuda
N
N
Akao
S
S
Takemura
G
G
Minatoguchi
S
S
Gotoh
K
K
Fujiwara
H
H
Fukuda
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D005707:Gallic Acid; D002945:Cisplatin