Abstract
Background:
Lung tumors express high levels of aromatase enzyme compared to surrounding normal tissue. Inhibition of aromatase has emerged as a recent therapeutic approach for the treatment of breast cancer. However, the role of aromatase inhibition in lung cancer treatment requires further investigation.
Methods:
The anti-proliferative effects of aromatase inhibitors were evaluated by MTT assay. Cell migration was assessed using wound healing assay. The mechanism of cell death was determined using annexin V-FITC/propidium iodide staining flow cytometry method. Cells' capability to form colonies was evaluated by soft agar colony formation assay.
Result:
Exemestane and curcumin significantly inhibited the growth of lung cancer cell lines in dose-and time- dependent manner. The IC50 values after 48 hours treatment with exemestane were 176, 180, and 120 µM in A549, H661and H1299, respectively. Curcumin IC50 values after 48 hours were 80, 43, and 68 µM in A549, H661and H1299, respectively. The combined treatment of exemestane or curcumin with cisplatin, raloxifene, and celecoxib resulted in a synergistic effect in A549 lung cell line with combination index of less than 1 suggesting synergism. Exemestane resulted in approximately 96% inhibition of wound closure at 100 µM in while curcumin resulted in approximately 63% inhibition wound closure at 50 µM. Exemestane and curcumin inhibited the formation of cell colonies by reducing the number and size of formed colonies of A549, H661 and H1299 cell lines in a concentration dependent manner. Exemestane and curcumin had significantly induced apoptosis in A549 cells compared to control of untreated cells.
Conclusion:
Aromatase inhibition by exemestane or curcumin had significantly inhibited the growth of lung cancer cell lines, synergized with cisplatin, raloxifene and celecoxib, suppressed lung cancer cell migratory potential, induced apoptosis, and reduced colony formation of lung cancer cells.
