Icariin induces apoptosis of human lung adenocarcinoma cells by activating the mitochondrial apoptotic pathway.

Lung cancer is the largest cause of morbidity and mortality among tumor diseases. Traditional first-line chemotherapeutic drugs are frequently accompanied by serious side effects when used to treat tumors, thus, novel drugs with reduced toxic effects may improve a patients' quality of life. Icariin, an extract of herba epimedii, has been demonstrated to exhibit multiple antitumor effects with low toxicity. In the present study, cell cycle analysis, apoptosis assays, DAPI staining, CCK8 assays, xenograft tumor models, mitochondrial membrane potential analysis, western blotting and reverse transcription-quantitative PCR were performed to determine the molecular mechanism underlying icariin activity in the human lung adenocarcinoma cell lines, A549 and H1975. The results showed that icariin reduced proliferation of A549 and H1975 cells in a time- and dose-dependent manner in vitro to a greater degree than the control BEAS-2B cells, and this was associated with increased apoptosis, but not with cell cycle progression. In vivo experiments showed that icariin treatment significantly decreased proliferation of H1975 cells in a xenograft mouse model. Mechanistically, icariin activated the mitochondrial pathway by inhibiting the activation of the PI3K-Akt pathway-associated kinase, Akt, resulting in the activation of members of the caspase family of proteins, and thus inducing apoptosis of A549 cells. Taken together, the results revealed that icariin has anti-cancer properties in lung cancer in vitro and in vivo without any noticeable toxic effects on normal lung epithelial cells. Icariin in combination with conventional anti-cancer agents may be an effective therapeutic strategy for treatment of lung carcinoma.