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Introduction
Lung cancer is becoming the leading cause of cancer-associated mortality worldwide, particularly in China (1,2). For patients with lung cancer, resistance to therapy is a common phenomenon, which threatens the success of the treatment currently used against the disease. Therefore, novel theraperutic strategies are required for the overcome tumor evasion.
Flavonoids are known for their wide spectrum of pharmacological properties, including antioxidant, antimicrobial and anticancer effects (3). Luteolin (3′,4′,5,7-tetra-hydroxyflavone) is a common dietary flavanoid, which, similar to several other flavanoids, exists in several traditional Chinese medicines (4). Luteolin has been demonstrated to exhibit anticancer properties, including the induction of apoptosis and cell cycle arrest, and the inhibition of metastasis and angiogenesis, in several cancer cell lines, including the A549 non-small lung cancer cell (5).
Sirt1 is a well-known NAD+-dependent class III protein deacetylase, which belongs to the silent information regulator family (6). This family has multiple functions and is critically involved in the stress responses, cellular metabolism and aging, through the deacetylation of a variety of substrates, including p53, forkhead-box transcription factors, PGC-1α, NF-κB, Ku70 and histones (7,8). Sirt1 negatively regulates the tumor suppressor p53 and other tumor suppressors (9) and inhibits the transcription activity of AP-1 by targeting c-JUN (10). However, the possible roles of SIRT1 in the regulation of the NCI-H460 human lung carcinoma cell apoptosis have not been reported. The present study investigated the anticancer effect of luteolin on NCI-H460 by SIRT1 on the regulation of cell apoptosis. This finding provides novel insight into the mechanisms of luteolin's anti-lung cancer effects.
Materials and methods
Reagents
Luteolin was obtained from Sigma-Aldrich (St. Louis, MO, USA) and was dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich) and adjusted to the final concentrations (20, 40, 80 and 160 µM) using complete RPMI-1640 medium. Paclitaxel (Taxol) was purchased from Haikou Pharmaceutical Factory Co., Ltd., (Haikou, China). The Taxol was diluted in serum-free culture media and was administered to cells at a final concentration of 300 nM. Fetal bovine serum (FBS), RPMI-1640 medium, Dulbecco's modified Eagle's medium (DMEM) and penicillin-streptomycin were purchased from Gibco Life Technologies (Grand Island, NY, USA). The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphnyl-2H-tet-razolium bromide (MTT) was obtained from Sigma-Aldrich. The primary and secondary antibodies used in the present study were obtained from Abcam (Cambridge, UK). All other...