Objective: To investigate the anticancer activity of Luteolin (Lu) and its synergism effect with bacillus calmette-guerin (BCG) on human bladder cancer cell line BIU-87.
Methods: Cultured BIU-87 cells were treated with different concentrations of Lu alone or the combination of Lu with BCG. MTT assay was used to measure the cell proliferation inhibition, and IC50 was calculated. Cell cycle and apoptosis were analyzed by flow cytometry with propidium iodide (PI) staining and Annexin-V FITC/PI dual parameter markers to clarify the mechanism of inhibiting cell proliferation and inducing apoptosis. Caspase-3 and phosphorylated c-Jun N-terminal kinases (P-JNK) expression were measured to detect the apoptosis signal pathways of Lu in cancer cells.
Results: Both Lu and BCG apparently inhibited the cell proliferation and induced the apoptosis dose-dependently, and microscope observation showed morphological changes in the apoptosis. Flow cytometry indicated that Lu arrested the cell cycle at G2 phase (P<0.05). It sensitized BCG-induced cytotoxicity and cell apoptosis, and upregulated expression of caspase-3 and activation of JNK (P<0.05).
Conclusion: As an effective anticancer agent, Lu can sensitize the effect of BCG by inducing the cell cycle arrest and apoptosis. This synergism effect is achieved by activation of caspase-3 and JNK. Combination of Lu with BCG may be one of the potential treatment for bladder cancer.