Anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer AGS cell line

• DOI: 10.1007/s11010-008-9749-x
• Publication Date: 2008-04-08T06:17:43Z
• Authors: Bin Wu; Qiang Zhang; Weiming Shen; Jun Zhu
• Keywords: 0303 health sciences; Cell Survival; Cell Cycle; Apoptosis; Cell Cycle Proteins; Drug Synergism; 3. Good health; 03 medical and health sciences; Stomach Neoplasms; Cell Line, Tumor; Humans; Cisplatin; Drug Screening Assays, Antitumor; Apoptosis Regulatory Proteins; Luteolin; Cell Proliferation

To investigate the anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer, gastric cancer AGS cells were treated with luteolin and/or other chemotherapeutic agents. Cell growth was assessed by MTT assay, cell cycle and apoptosis were assessed by flow-cytometric analysis, and the expression of major proteins regulating cell cycle and apoptosis was also detected. The results showed that luteolin inhibited the growth of gastric cancer cells in a dose- and time-dependent manner. Flow cytometry revealed that the percentage of cells at G2/M phase increased dose-dependently. The protein levels of Cdc2, Cyclin B1 and Cdc25C were reduced and p21/cip1 was up-regulated after the treatment with luteolin. Furthermore, luteolin induced apoptosis in gastric cancer AGS cells. Western blotting showed that luteolin treatment significantly increased the levels of pro-apoptotic proteins, including Caspase-3, 6, 9, Bax, and p53, and decreased the levels of anti-apoptotic protein Bcl-2, thus shifting the Bax/Bcl ratio in favor of apoptosis. It was also demonstrated that a combinational treatment of cisplatin and luteolin induced more effectively cell growth inhibition, compared to cisplatin treatment alone. These findings indicate the anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer AGS cells and luteolin may be a promising candidate agent used in the treatment of gastric cancer.