Content area
Full Text
Introduction
Lung cancer remains the leading cause of cancer-associated mortality, annually resulting in >1,000,000 mortalities globally in 2012 (1). Additionally, ~1,200,000 new cases are diagnosed every year and prognoses of lung cancer are poor, as estimated worldwide in 2012 (2). Lung adenocarcinoma is the predominant histological subtype of non-small lung cancer (3). The mean 5-year survival rate of lung adenocarcinoma is <15% in the urban areas of China as estimated in 2015, primarily due to the late-stage detection and a paucity of late-stage treatments (4). The availability of effective anticancer drugs is considered to be the key for improvement in the treatment of lung adenocarcinoma.
7, 8-Diacetoxy-4-methylcoumarin (DAMTC) is a thioderivative of 4-methyl coumarin (5). Coumarins belong to the flavonoid class of plant secondary metabolite, which have been demonstrated to exhibit diverse and beneficial biological activities, including antitumoral, anticoagulant and anti-inflammatory properties (5). Natural coumarins or synthetic analogs have attracted intense interest for their applicability as drugs (6). They have been determined to have a variety of therapeutic applications, including antitumor and anti-human immunodeficiency virus therapy (7), and antioxidant (8) and antibacterial (9) applications. Lacy and O'Kennedy (10) demonstrated that genistein and esculetin could exert the most potent inhibitory effect on cell growth of two cell lines, A549, a lung carcinoma cell line, and MCF-7, a breast carcinoma cell line. Previously, the coumarin derivative DAMTC was indicated to inhibit cellular proliferation and induce apoptosis on human non-small cell lung cancer A549 cells (11). Furthermore, the observations of Goel et al (12) reported that upregulation of the nuclear factor-κB, p53 and Akt pathways, and downregulation of the mitogen activated protein kinase (MAPK) and Cox-2 pathways were involved in the molecular mechanism of apoptosis induction by DAMTC in A549 cells. However, the mechanisms of the anti-proliferative effects of DAMTC in lung adenocarcinoma are incompletely defined, and further insights into the mechanisms are required.
Previously, Goel et al (1) used the integrated proteomics and transcriptomics approach, and identified that DAMTC could regulate cell motility and cytoskeletal reorganization in lung adenocarcinoma. In the present study, differentially-expressed genes (DEGs) were identified in DAMTC-treated lung adenocarcinoma, compared with DAMTC-untreated controls, using the same gene expression profile. Comprehensive bioinformatics were used to analyze the significant pathways and functions, and to construct...