Curcumin Induces Apoptosis in Human Non-small Cell Lung Cancer NCI-H460 Cells through ER Stress and Caspase Cascade- and Mitochondria-dependent Pathways

Division of Critical Care Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan, ROC.
Anticancer research (Impact Factor: 1.83). 06/2010; 30(6):2125-33.
Source: PubMed


It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.

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    • "Lung cancer is one of the major health issues and is among the top 20 causes of death in the entire world, occurring in both genders and at different ages (El-Telbany and Ma, 2012; Ferlay et al., 2010; Kastner et al., 2012; Wu et al., 2010). After cardiovascular diseases and motor vehicle accidents, cancers are the most widespread causes of death in Iran, among which lung cancer is the second one (Saadat et al., 2014). "
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    ABSTRACT: Exposure to arsenic is one of the major causes of lung cancer due to production of Reactive Oxygen Species (ROS). Herbal medicine is a new approach used for prevention or treatment of cancers. Among various herbal compounds, a lot of attention has been paid to curcumin, as antioxidant, anti-proliferative, anti-carcinogenic and anti-tumor and pro-apoptotic properties of curcumin have been well studied. In the present study, we investigated the effects of curcumin on lung cancer cell lines and arsenic-treated lung cancer cell lines, originated from different stages of lung cancer development. Here, we measured ROS generation and caspase 3/7 activity for both curcumin-treated cell lines and those co-treated with arsenic and curcumin. Then, we studied lipid peroxidation, intracellular ATP content, and cytochrome c release to further investigate how ROS generation and curcumin exert synergistic effects and direct cells toward apoptosis. According to our data, curcumin has a dual effect on ROS generation which is dependent on specific concentration as a threshold and seems to induce apoptosis by two different mechanisms. Moreover, for the first time we report that curcumin delays the drop in ATP levels in these cell lines and hence provides required energy for apoptosis process. Furthermore, western blot analysis reveals that release of cytochrome c is highest when ATP begins to drop in the presence of curcumin. To sum it up, it seems that curcumin is strong candidate for prevention or treatment of lung cancer, especially at stage 2.
    Full-text · Article · Nov 2015 · European journal of pharmacology
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    • "enhance bioavailability. Overwhelmingly, mechanisms of action reported for the antitumor efficacy of curcumin in lung cancer cells are via mitochondrial-mediated cell death elicited by an increase in the Bax:B cell lymphoma-2 ratio or by an increase in intracellular reactive oxygen species (ROS) (Chanvorachote et al., 2009; Pongrakhananon et al., 2010; Saha et al., 2010; Wu et al., 2010; Wang et al., 2011, 2013b; Sahoo et al., 2012; Yang et al., 2012a,b; Li et al., 2013; Liu et al., 2013; Xiao et al., 2013; Chen et al., 2014). Migration and invasive capacity of lung cancer cells may be further decreased by inhibition of matrix metalloprotease expression, decreased nuclear factor-kB, EGFR, Akt, signal transducer and activator of transcription 3, and Cdc42 signaling (Chen et al., 2004, 2012, 2014; Lee et al., 2005; Lin et al., 2009, 2012; Puliyappadamba et al., 2010; Kaushik et al., 2012; Liu et al., 2013; Yamauchi et al., 2014; Zhou et al., 2013a; Li et al., 2014b). "
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    Full-text · Article · Jun 2014 · Journal of Pharmacology and Experimental Therapeutics
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    • "Curcumin (diferuloylmethane), the dietary polyphenol constituent of the perennial herb Curcuma longa (popularly known as turmeric), exhibits wide range of bioactivities including antioxidant , anti-inflammatory, anti-cancer, anti-angiogenic and antimicrobial properties [1]. Curcumin's chemopreventive characteristics , in particular, have been demonstrated against a wide range of cancers including bladder [2], cervical [3], lung [4] [5], pancreatic [6], colorectal [7] cancers, etc. Despite curcumin's remarkable nontoxic nature [7], extremely low water solubility and poor bioavailability are impeding its effective clinical use [8] [9]. "
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    ABSTRACT: Curcumin, because of its distinguishing ability to inhibit activation of transcription factor linked to chemoresistance and drug transporters, is now being co-administered with various potent anti-cancer drugs. In the present study, we report on such potentiating capabilities of curcumin in anti-angiogenic cancer therapy. With a view to simultaneously deliver curcumin and doxorubicin to tumor vasculature in anti-angiogenic cancer therapy, herein we report on the design & synthesis of a tumor vasculature targeting pegylated RGDK-lipopeptide. We show that curcumin & doxorubicin co-encapsulated within the liposomes of the presently described pegylated RGDK-lipopeptide exhibit synergism in inhibiting proliferation, invasion and migration of both tumor and endothelial cells presumably by inhibiting proliferation and metastasis related genes both at mRNA & protein levels. Pronounced tumor growth inhibition was observed in mice treated with formulations containing both the drugs. Tumor growth inhibition was found to be 2-3 folds less in mice treated with formulations containing only curcumin or only doxorubicin. The presently described liposomal system is expected to find future use for simultaneously delivering potentially any combinations of hydrophilic and hydrophobic potent small molecule cancer therapeutics to tumor vasculature in anti-angiogenic cancer therapy.
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