Cs analysis: QK. Drafted the manuscript: QK. Performed the testified experiments

Cs analysis: QK. Drafted the manuscript: QK. Performed the testified experiments: LFL JZP. Revised the paper: XJW. Supervised the work: XJW. Conceived and designed the experiments: XJW JZP QK. Performed the experiments: QK. Contributed reagents/ materials/analysis tools: SLS.
Lung cancer is responsible for more cancer deaths in the United States than the combined mortality of colorectal, breast and prostate cancer [1]. Even with the newer advanced therapeutic approaches, the 5-year overall survival rate is less than 16 and has not changed appreciably over many decades [1,2]. This poor prognosis emphasizes the urgent need for the development of novel strategies for the prevention and more effective treatment of this deadly disease. Natural products (NPs) are widely used by Americans as complementary and alternative medications (CAM) for the prevention and treatment of various human diseases including cancers [3,4]. The use of NPs as antitumor agents for the management of human cancers is an attractive idea because they are readily available and exhibit little or no toxicity [3,5?]. Resveratrol (RV) is one of such NPs and has been shown to exhibit both anticancer and Linolenic acid methyl ester chemopreventive potentials [3,8?0]. However, the exact molecular mechanisms underlying RV’s chemopreventive and anticancer effects are not completely understood. The goal of this study was to define the role of premature MedChemExpress LED-209 senescence in RV-induced antitumor effects in lung cancer cells. Cellular senescence is a state of permanent cell cycle arrest that can be triggered by a variety of stresses including DNA damage,telomere shortening and oxidative stress [11?3]. The two major categories of cellular senescence are replicative senescence and stress-induced premature senescence (SIPS). Replicative senescence was first described by Hayflick and Moorhead in human fibroblasts after cells underwent extensive replication as a consequence of serial culture passages [14]. Subsequently, it was found that cells also can undergo SIPS in response to DNAdamaging agents such as ionizing radiation and anticancer chemotherapeutics [11?3,15]. Cells undergoing SIPS are morphologically indistinguishable from replicatively senescent cells and exhibit many of the characteristics ascribed to replicative senescence, such as increased senescence associated b-galactosidase (SA-b-gal) activity and increased p53 and p21 expression [11?3,15?7]. Although telomere shortening was thought to be the major cause for replicative senescence, premature senescence can occur in a telomerase- and telomere shortening-independent mechanism [18,19]. Senescence limits the life span and proliferative capacity of cells, therefore the induction of senescence is regarded as an important mechanism of cancer prevention [20?22]. More importantly, emerging evidence has demonstrated that therapy-induced senescence is a critical mechanism through which many anticancer agents inhibit the growth of tumor cells [11,12,23]. Interestingly, it has been shown that therapy-inducedResveratrol-Induced Senescence in Cancer CellsFigure 1. RV inhibits the growth of NSCLC cells in a dose-dependent manner. (A) Clonogenic survival assays show that the number of cancer cell-derived colonies decreases with RV dose. (B) The results of clonogenic assays were normalized to the clonogenic survival of control A549 cells and are expressed as of control. (C) The results of clonogenic assays were normalized to the clonogenic survival of control H460 cells.Cs analysis: QK. Drafted the manuscript: QK. Performed the testified experiments: LFL JZP. Revised the paper: XJW. Supervised the work: XJW. Conceived and designed the experiments: XJW JZP QK. Performed the experiments: QK. Contributed reagents/ materials/analysis tools: SLS.
Lung cancer is responsible for more cancer deaths in the United States than the combined mortality of colorectal, breast and prostate cancer [1]. Even with the newer advanced therapeutic approaches, the 5-year overall survival rate is less than 16 and has not changed appreciably over many decades [1,2]. This poor prognosis emphasizes the urgent need for the development of novel strategies for the prevention and more effective treatment of this deadly disease. Natural products (NPs) are widely used by Americans as complementary and alternative medications (CAM) for the prevention and treatment of various human diseases including cancers [3,4]. The use of NPs as antitumor agents for the management of human cancers is an attractive idea because they are readily available and exhibit little or no toxicity [3,5?]. Resveratrol (RV) is one of such NPs and has been shown to exhibit both anticancer and chemopreventive potentials [3,8?0]. However, the exact molecular mechanisms underlying RV’s chemopreventive and anticancer effects are not completely understood. The goal of this study was to define the role of premature senescence in RV-induced antitumor effects in lung cancer cells. Cellular senescence is a state of permanent cell cycle arrest that can be triggered by a variety of stresses including DNA damage,telomere shortening and oxidative stress [11?3]. The two major categories of cellular senescence are replicative senescence and stress-induced premature senescence (SIPS). Replicative senescence was first described by Hayflick and Moorhead in human fibroblasts after cells underwent extensive replication as a consequence of serial culture passages [14]. Subsequently, it was found that cells also can undergo SIPS in response to DNAdamaging agents such as ionizing radiation and anticancer chemotherapeutics [11?3,15]. Cells undergoing SIPS are morphologically indistinguishable from replicatively senescent cells and exhibit many of the characteristics ascribed to replicative senescence, such as increased senescence associated b-galactosidase (SA-b-gal) activity and increased p53 and p21 expression [11?3,15?7]. Although telomere shortening was thought to be the major cause for replicative senescence, premature senescence can occur in a telomerase- and telomere shortening-independent mechanism [18,19]. Senescence limits the life span and proliferative capacity of cells, therefore the induction of senescence is regarded as an important mechanism of cancer prevention [20?22]. More importantly, emerging evidence has demonstrated that therapy-induced senescence is a critical mechanism through which many anticancer agents inhibit the growth of tumor cells [11,12,23]. Interestingly, it has been shown that therapy-inducedResveratrol-Induced Senescence in Cancer CellsFigure 1. RV inhibits the growth of NSCLC cells in a dose-dependent manner. (A) Clonogenic survival assays show that the number of cancer cell-derived colonies decreases with RV dose. (B) The results of clonogenic assays were normalized to the clonogenic survival of control A549 cells and are expressed as of control. (C) The results of clonogenic assays were normalized to the clonogenic survival of control H460 cells.