Induction of apoptosis by gallic acid in lung cancer cells.
The apoptosis-inducing effect of gallic acid (3,4,5-trihydroxybenzoic acid) was investigated in four human lung cancer cell lines, SBC-3 (small cell carcinoma), EBC-1 (squamous cell carcinoma), A549 (adenocarcinoma) and SBC-3/CDDP (cisplatin-resistant subclone of SBC-3). Gallic acid induced apoptosis in a dose-dependent manner as evidenced by analyses of DNA fragmentation, changes in cell morphology and loss of viability. Fifty percent inhibitory concentration (IC50) values of gallic acid on the cell viability of SBC-3, EBC-1 and A549 were around 10, 20 and 60 microg/ml, respectively. The IC50 value for SBC-3/CDDP cells was almost the same as that of SBC-3, suggesting that susceptibility of cells to gallic acid-induced apoptosis is not altered by the acquisition of cisplatin resistance. The apoptotic process was effectively triggered by 30 min exposure to gallic acid. A caspase inhibitor and alpha-tocopherol effectively prevented the gallic acid-induced apoptosis, indicating the involvememt of caspase activation and oxidative processes during the course of apoptosis in gallic acid-treated cancer cells. These findings suggest the possible applicability of gallic acid in lung cancer therapy, especially to circumvent resistance to anti-cancer drugs.
Ohno
Y
Y
Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
Fukuda
K
K
Takemura
G
G
Toyota
M
M
Watanabe
M
M
Yasuda
N
N
Xinbin
Q
Q
Maruyama
R
R
Akao
S
S
Gotou
K
K
Fujiwara
T
T
Fujiwara
H
H
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005707:Gallic Acid / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology
D000970:Antineoplastic Agents; D014810:Vitamin E; D005707:Gallic Acid; D002945:Cisplatin