title: Formononetin suppresses the proliferation of human non-small cell lung cancer through induction of cell cycle arrest and apoptosis.
abstract: Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus and possesses antitumorigenic properties. In the present study, we investigated the anti-proliferative effects of formononetin on human non-small cell lung cancer (NSCLC), and further elucidated the molecular mechanism underlying the anti-tumor property. MTT assay showed that formononetin treatment significantly inhibited the proliferation of two NSCLC cell lines including A549 and NCI-H23 in a time- and dose-dependent manner. Flow cytometric analysis demonstrated that formononetin induced G1-phase cell cycle arrest and promoted cell apoptosis in NSCLC cells. On the molecular level, we observed that exposure to formononetin altered the expression levels of cell cycle arrest-associated proteins p21, cyclin A and cyclin D1. Meanwhile, the apoptosis-related proteins cleaved caspase-3, bax and bcl-2 were also changed following treatment with formononetin. In addition, the expression level of p53 was dose-dependently upregulated after administration with formononetin. We also found that formononetin treatment increased the phosphorylation of p53 at Ser15 and Ser20 and enhances its transcriptional activity in a dose-dependent manner. Collectively, these results demonstrated that formononetin might be a potential chemopreventive drug for lung cancer therapy through induction of cell cycle arrest and apoptosis in NSCLC cells.
authors: Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai 200030, China.
authors: Yi
authors: Y
authors: Yang
authors: Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai 200030, China.
authors: Yi
authors: Y
authors: Zhao
authors: Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai 200030, China.
authors: Xinghao
authors: X
authors: Ai
authors: Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai 200030, China.
authors: Baijun
authors: B
authors: Cheng
authors: Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai 200030, China.
authors: Shun
authors: S
authors: Lu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D008517:Phytotherapy / Q000379:methods
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; C007768:formononetin
keywords: Human non-small cell lung cancer; apoptosis; cell cycle; formononetin; proliferation