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).
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.
Available from: Lynne Howells
- "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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ABSTRACT: Lung cancer is responsible for over 1 million deaths worldwide each year. Smoking cessation for lung cancer prevention remains key, but it is increasingly acknowledged that prevention strategies also need to focus on high risk groups including ex-smokers, and patients who have undergone resection of a primary tumor. Models for chemoprevention of lung cancer often present conflicting results, making rational design of lung cancer chemoprevention trials challenging. There has been much focus on use of dietary bioactive compounds in lung cancer prevention strategies, primarily due to their favorable toxicity profile and long history of use within the human populace. One such compound is curcumin, derived from the spice turmeric. This review summarises and stratifies pre-clinical evidence for chemopreventive efficacy of curcumin in models of lung cancer, and adjudges the weight of evidence for use of curcumin in lung cancer chemoprevention strategies.
Journal of Pharmacology and Experimental Therapeutics 06/2014; 350(3). DOI:10.1124/jpet.114.216333 · 3.97 Impact Factor
Available from: Soumen Saha
- "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 . Curcumin's chemopreventive characteristics , in particular, have been demonstrated against a wide range of cancers including bladder , cervical , lung  , pancreatic , colorectal  cancers, etc. Despite curcumin's remarkable nontoxic nature , extremely low water solubility and poor bioavailability are impeding its effective clinical use  . "
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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.
Biomaterials 11/2013; 35(5). DOI:10.1016/j.biomaterials.2013.10.074 · 8.56 Impact Factor
Available from: PubMed Central
- "Its anti-cancer effect has been seen in a few clinical trials, mainly as a native chemoprevention agent in colon and pancreatic cancer . Recently, it was reported that curcumin exerts its pro-apoptotic effects by inducing ER stress in several tumor cells, including acute promyelocytic leukemia cells , human non-small cell lung cancer H460 cells , and human liposarcoma cells . Although curcumin has an evident anti-cancer activity, rapid metabolism and low bioavailability have been highlighted as the major limitations in therapeutic applications . "
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ABSTRACT: Recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy.
A bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, the in vivo anti-tumor effect of B82 was evaluated.
B82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cells in vitro and inhibited H460 tumor growth in vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress both in vitro and in vivo.
A new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC.
BMC Cancer 10/2013; 13(1):494. DOI:10.1186/1471-2407-13-494 · 3.36 Impact Factor
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