Diallyl trisulfide inhibits gastric cancer stem cell properties through ΔNp63/sonic hedgehog pathway.

Gastric cancer is one of the deadliest malignant tumors, and half of the patients develop recurrences or metastasis within 5 years after eradication therapy. Cancer stem cells (CSCs) are considered to be important in this progress. The sonic hedgehog (SHH) pathway plays an important role in the maintenance of gastric CSCs characteristics. The p63 proteins are vital transcription factors belonging to the p53 family, while their functions in regulating CSCs remain unclear. The preventive effects of dietary diallyl trisulfide (DATS) against human gastric cancer have been verified. However, whether DATS can target gastric CSCs are poorly understood. Here, we investigated the role of ΔNp63/SHH pathway in gastric CSCs and the inhibitory effect of DATS on gastric CSCs via ΔNp63/SHH pathway. We found that ΔNp63 was upregulated in serum-free medium cultured gastric tumorspheres compared with the parental cells. Overexpression of ΔNp63 elevated the self-renewal capacity and CSC markers' levels in gastric sphere-forming cells. Furthermore, we found that ΔNp63 directly bound to the promoter region of Gli1, the key transcriptional factor of SHH pathway, to enhance its expression and to activate SHH pathway. In addition, it was revealed that DATS effectively inhibited gastric CSC properties both in vitro and in vivo settings. Activation of SHH pathway attenuated the suppressive effects of DATS on the stemness of gastric cancer. Moreover, DATS suppression of gastric CSC properties was also diminished by ΔNp63 upregulation through SHH pathway activation. These findings illustrated the role of ΔNp63/SHH pathway in DATS inhibition of gastric cancer stemness. Taken together, the present study suggested for the first time that DATS inhibited gastric CSCs properties by ΔNp63/SHH pathway.

Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway.

BACKGROUND: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. METHODS: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. RESULTS: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10-9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10-9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. CONCLUSION: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.

Super-Resolution Imaging of Mitochondrial HClO during Cell Ferroptosis Using a Near-Infrared Fluorescent Probe.

Ferroptosis is of great importance in physiological and pathological processes, which is associated with various inflammation-related diseases, cardiovascular diseases, and even cancer. Ferroptosis can cause abnormal change of reactive oxygen species (ROS) in mitochondria. Hypochlorous acid (HClO) acts as a typical ROS. Therefore, it is needed to study the relationship between mitochondrial morphology and HClO changes during ferroptosis at the subcellular level. To this end, a near-infrared-excitation/emission fluorescent probe, HD-Br-1, for rapid detection of mitochondrial HClO was developed based on the specific oxidative cleavage of the N,N-dimethylthiocarbamate moiety. The fluctuation in mitochondrial HClO content and the change in mitochondrial morphology during ferroptosis were monitored in real time by super-resolution imaging. In addition, HD-Br-1 was successfully applied to monitor exogenous and endogenous mitochondrial HClO during cell ferroptosis and visualize tumor to discriminate from healthy tissues. Therefore, we believe that HD-Br-1 could provide a valuable approach for the detection of mitochondrial HClO in cancer cells as well as for understanding the ferroptosis mechanism and early diagnosis of cancers associated with ferroptosis for future research.

Progress of metabolic engineering for the production of eicosapentaenoic acid.

Eicosapentaenoic Acid (EPA) is an essential ω-3 polyunsaturated fatty acid for human health. Currently, high-quality EPA production is largely dependent on the extraction of fish oil, but this unsustainable approach cannot meet its rising market demand. Biotechnological approaches for EPA production from microorganisms have received increasing attention due to their suitability for large-scale production and independence of the seasonal or climate restrictions. This review summarizes recent research on different microorganisms capable of producing EPA, such as microalgae, bacteria, and fungi, and introduces the different EPA biosynthesis pathways. Notably, some novel engineering strategies have been applied to endow and improve the abilities of microorganisms to synthesize EPA, including the construction and optimization of the EPA biosynthesis pathway, an increase in the acetyl-CoA pool supply, the increase of NADPH and the inhibition of competing pathways. This review aims to provide an updated summary of EPA production.

Interleukin-17A mediates tobacco smoke-induced lung cancer epithelial-mesenchymal transition through transcriptional regulation of ΔNp63α on miR-19.

Interleukin-17A (IL-17A) is an essential inflammatory cytokine in the progress of carcinogenesis. Tobacco smoke (TS) is a major risk factor of lung cancer that influences epithelial-mesenchymal transition (EMT) process. However, the potential mechanism by which IL-17A mediates the progression of lung cancer in TS-induced EMT remains elusive. In the present study, it was revealed that the IL-17A level was elevated in lung cancer tissues, especially in tumor tissues of cases with experience of smoking, and a higher IL-17A level was correlated with induction of EMT in those specimens. Moreover, the expression of ΔNp63α was increased in IL-17A-stimulated lung cancer cells. ΔNp63α functioned as a key oncogene that bound to the miR-17-92 cluster promoter and transcriptionally increased the expression of miR-19 in lung cancer cells. Overexpression of miR-19 promoted EMT in lung cancer with downregulation of E-cadherin and upregulation of N-cadherin, while its inhibition suppressed EMT. Finally, the upregulated levels of IL-17A, ΔNp63α, and miR-19 along with the alteration of EMT-associated biomarkers were found in lung tissues of TS-exposed mice. Taken together, the abovementioned results suggest that IL-17A increases ΔNp63α expression, transcriptionally elevates miR-19 expression, and promotes TS-induced EMT in lung cancer. These findings may provide a new insight for the identification of therapeutic targets for lung cancer.

Bacterial mandelic acid degradation pathway and its application in biotechnology.

Mandelic acid and its derivatives are an important class of chemical synthetic blocks, which is widely used in drug synthesis and stereochemistry research. In nature, mandelic acid degradation pathway has been widely identified and analysed as a representative pathway of aromatic compounds degradation. The most studied mandelic acid degradation pathway from Pseudomonas putida consists of mandelate racemase, S-mandelate dehydrogenase, benzoylformate decarboxylase, benzaldehyde dehydrogenase and downstream benzoic acid degradation pathways. Because of the ability to catalyse various reactions of aromatic substrates, pathway enzymes have been widely used in biocatalysis, kinetic resolution, chiral compounds synthesis or construction of new metabolic pathways. In this paper, the physiological significance and the existing range of the mandelic acid degradation pathway were introduced first. Then each of the enzymes in the pathway is reviewed one by one, including the researches on enzymatic properties and the applications in biotechnology as well as efforts that have been made to modify the substrate specificity or improving catalytic activity by enzyme engineering to adapt different applications. The composition of the important metabolic pathway of bacterial mandelic acid degradation pathway as well as the researches and applications of pathway enzymes is summarized in this review for the first time.

Magnesium isoglycyrrhizinate ameliorates lipopolysaccharide-induced liver injury by upregulating autophagy and inhibiting inflammation via IL-22 expression.

Liver disease has become a major cause of premature mortality worldwide. It is well known that dysregulated inflammation response plays a crucial role in most liver diseases. As a Chinese medicinal herb, Magnesium isoglycyrrhizinate (MgIG) has been proven to have good hepatoprotective activity and has been used in clinic to treat liver disease. However, the mechanisms by which MgIG regulates LPS-induced liver injury and inflammation in vivo remain elusive. In our study, MgIG pretreatment mitigated LPS-induced liver damage by suppressing apoptosis and inflammation via regulating macrophage/neutrophil infiltration. MgIG ameliorated the effects of LPS on pro-oxidant enzymes (NOX1/2/4) and anti-oxidant enzymes (SOD1/2). Interestingly, we found that the level of the hepatoprotective cytokine interleukin (IL)-22 was significantly upregulated in MgIG-treated liver tissues, which might be a potential mechanism of MgIG against liver injury. Moreover, we found that MgIG treatment not only inhibited TLR4/MyD88/NF-κB signaling pathway, but also activated autophagy. Furthermore, IL-22 treatment activated autophagy and inhibited TLR4/NF-κB signaling pathway in vitro, suggesting that IL-22-activated autophagy and -inhibited inflammation also participated in the protective effects of MgIG. Altogether, our results uncovered the potential mechanisms of the hepatoprotective effects of MgIG, which provided critical evidence to support the use of MgIG to prevent and treat liver diseases.

Strategies for enhancing terpenoids accumulation in microalgae.

Terpenoids represent one of the largest class of chemicals in nature, which play important roles in food and pharmaceutical fields due to diverse biological and pharmacological activities. Microorganisms are recognized as a promising source of terpenoids due to its short growth cycle and sustainability. Importantly, microalgae can fix inorganic carbon through photosynthesis for the growth of themselves and the biosynthesis of various terpenoids. Moreover, microalgae possess effective biosynthesis pathways of terpenoids, both the eukaryotic mevalonic acid (MVA) pathway and the prokaryotic methyl-D-erythritol 4-phosphate (MEP) pathway. In recent years, various genetic engineering strategies have been applied to increase target terpenoid yields, including overexpression of the rate-limited enzymes and inhibition of the competing pathways. However, since gene-editing tools are only built in some model microalgae, fermentation strategies that are easier to be operated have been widely successful in promoting the production of terpenoids, such as changing culture conditions and addition of chemical additives. In addition, an economical and effective downstream process is also an important consideration for the industrial production of terpenoids, and the solvent extraction and the supercritical fluid extraction method are the most commonly used strategies, especially in the industrial production of ß-carotene and astaxanthin from microalgae. In this review, recent advancements and novel strategies used for terpenoid production are concluded and discussed, and new insights to move the field forward are proposed. KEY POINTS: • The MEP pathway is more stoichiometrically efficient than the MVA pathway. • Advanced genetic engineering and fermentation strategies can increase terpene yield. • SFE has a higher recovery of carotenoids than solvent extraction.

Curcumin potentiates laryngeal squamous carcinoma radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.

Context: Curcumin has shown efficacy in promoting radiosensitivity combined with radiotherapy. However, the role and mechanism of curcumin on radiosensitivity in laryngeal squamous cell cancer (LSCC) is largely unknown.Objective: The aim of our study is to explore the role of IKKγ-NF-κB signaling in curcumin enhancing LSCC cell radiosensitivity in vitro.Materials and methods: Curcumin and X-ray were used to induce cell DNA damage and apoptosis, or inhibit cell clone formation. IKKγ siRNA and plasmid were used to change IKKγ expression. The CCK8 assay was used to detect cell viability. Clone formation ability was analyzed using a clonogenic assay, cell apoptosis was examined using flow cytometry, an immunofluorescence assay was used to detect DNA damage, while mRNA and protein levels were assayed using real time PCR and western blotting, respectively.Results: Curcumin significantly enhanced irradiation-induced DNA damage and apoptosis, while weakening clone-forming abilities of LSCC cell line Hep2 and Hep2-max. Compared to Hep2 cells, Hep2-max cells are more sensitive to curcumin post-irradiation. Curcumin suppressed irradiation-induced NF-κB activation by suppressing IKKγ expression, but not IKKα and IKKß. Overexpression of IKKγ decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKKγ overexpression further increased expression of NF-κB downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKKγ silencing enhanced irradiation-induced DNA damage and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKKγ silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1.Conclusions: Curcumin enhances LSCC radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.

Modulation of miR-34a in curcumin-induced antiproliferation of prostate cancer cells.

Curcumin is a phytochemical which exhibits significant inhibitory effect in multiple cancers including prostate cancer. MicroRNA-34a (miR-34a) was found to be a master tumor suppressor miRNA and regulated the growth of cancer cells. To date, however, the role of miR-34a in the anticancer action of curcumin against prostate cancer has been rarely reported. In the present study, we showed that curcumin altered the expression of cell cycle-related genes (cyclin D1, PCNA, and p21) and inhibited the proliferation of prostate cancer cells. Furthermore, we found that curcumin significantly upregulated the expression of miR-34a, along with the downregulated expression of ß-catenin and c-myc in three prostate cancer cell lines. Inhibition of miR-34a activated ß-catenin/c-myc axis, altered cell cycle-related genes expression and significantly suppressed the antiproliferation effect of curcumin in prostate cancer cells. Findings from this study revealed that miR-34a plays an important role in the antiproliferation effect of curcumin in prostate cancer.

Magnesium isoglycyrrhizinate suppresses LPS-induced inflammation and oxidative stress through inhibiting NF-κB and MAPK pathways in RAW264.7 cells.

Magnesium Isoglycyrrhizinate (MgIG), a novel molecular compound extracted from licorice root, has exhibited greater anti-inflammatory activity and hepatic protection than glycyrrhizin and ß-glycyrrhizic acid. In this study, we investigated the anti-inflammatory effect and the potential mechanism of MgIG on Lipopolysaccharide (LPS)-treated RAW264.7 cells. MgIG down-regulated LPS-induced pro-inflammatory mediators and enzymes in LPS-treated RAW264.7 cells, including TNF-α, IL-6, IL-1ß, IL-8, NO and iNOS. The generation of reactive oxygen species (ROS) in LPS-treated RAW264.7 cells was also reduced. MgIG attenuated NF-κB translocation by inhibiting IKK phosphorylation and IκB-α degradation. Simultaneously, MgIG also inhibited LPS-induced activation of MAPKs, including p38, JNK and ERK1/2. Taken together, these results suggest that MgIG suppresses inflammation by blocking NF-κB and MAPK signaling pathways, and down-regulates ROS generation and inflammatory mediators.

Diallyl Trisulfide inhibits breast cancer stem cells via suppression of Wnt/ß-catenin pathway.

Cancer stem cells (CSCs) play a central role in the development of breast cancer. The canonical Wnt/ß-catenin signal pathway is critical for maintaining CSCs characteristics. Diallyl trisulfide (DATS), a natural organosulfur compound from the garlic, exhibits effective antitumor properties. However, the role of DATS in regulating breast CSCs activity and the underlying molecular mechanisms remain obscure. In the present study, we reported that DATS efficiently inhibited the viability of breast CSCs as evidenced by reducing turmorspheres formation, decreasing the expression of breast CSCs markers (CD44, ALDH1A1, Nanog, and Oct4), as well as inhibiting proliferation and inducing apoptosis. Furthermore, we showed that DATS downregulated the activity of Wnt/ß-catenin pathway, while LiCl-triggered Wnt/ß-catenin activation diminished DATS inhibition on breast CSCs. Taken together, our results illustrated that DATS suppressed breast CSCs through inhibiting Wnt/ß-catenin pathway activation. These novel findings could provide new insights into the molecular mechanisms of breast CSCs regulation as well as its target intervention and might provide new strategies for preventing and treating breast cancers.

P53 modulates hepatic insulin sensitivity through NF-κB and p38/ERK MAPK pathways.

Besides its well-established oncosuppressor activity, the role of p53 in regulating metabolic pathways has been recently identified. Nevertheless, the function of p53 with respect to insulin resistance appears highly controversial. To address this issue, we investigated the expression of p53 in experimental model of insulin resistance. Then we used activator (nutlin-3α) and inhibitor (pifithrin-α, PFT-α) of p53 in HepG2 cell. Here we showed that p53 protein level was decreased in the hepatic tissue of high-fat diet-induced insulin resistance mice, genetically diabetic ob/ob mice and palmitate (PA) treated HepG2 cells. And high expression of phosphor-p38, ERK1/2 and nuclear factor kappa B (NF-κB) p65 accompanied with low expression of p53. But activation of p53 with nutlin-3α prevented PA-induced reduction of glucose consumption and suppression of insulin signaling pathways. At the same time, nutlin-3α downregulated the activation of NF-κB, p38 and ERK1/2 pathways upon stimulation with PA. In contrast, inhibition of p53 with PFT-α decreased glucose consumption and suppressed insulin signaling pathway. Furthermore, PFT-α activated NF-κB, p38 and ERK1/2 pathways in HepG2 cells. Overall, these results suggest that p53 is involved in improving insulin sensitivity of hepatic cells via inhibition of mitogen-activated protein kinases (MAPKs) and NF-κB pathways.

Sonic hedgehog and Wnt/ß-catenin pathways mediate curcumin inhibition of breast cancer stem cells.

Cancer stem cells (CSCs) play an essential role in the progression of many tumors. Sonic hedgehog (Shh) and Wnt/ß-catenin pathways are crucial in maintaining the stemness of CSCs. Curcumin has been shown to possess anticancer activity. However, the interventional effect of curcumin on breast CSCs has not been elucidated. In the present study, we investigated the role of Shh and Wnt/ß-catenin pathway in curcumin inhibition of breast CSCs. We showed that the levels of breast CSCs markers were significantly elevated in SUM159 and MCF7 sphere-forming cells. We further illustrated that curcumin effectively decreased breast CSCs activity by inhibiting tumor sphere formation, decreasing breast CSCs markers (CD44, ALDH1A1, Nanog, and Oct4), as well as inhibiting proliferation and inducing apoptosis. Moreover, we showed that downregulation of Shh and Wnt/ß-catenin activity resulted in breast CSCs inhibition; curcumin exerted an inhibitory effect on breast CSCs by suppressing both Shh and Wnt/ß-catenin pathways. Taken together, these results indicated curcumin inhibition of breast CSCs by downregulation of Shh and Wnt/ß-catenin pathways. Findings from this study could provide new insights into the potential therapeutic application of curcumin in breast CSCs elimination and cancer intervention.

Modulation of autophagy in the protective effect of resveratrol on PM2.5-induced pulmonary oxidative injury in mice.

Ambient fine particulate matter (PM2.5) is capable of inducing pulmonary oxidative injury. Autophagy maintains basal cellular homeostasis and plays a critical role in the pathogenesis of lung diseases. Resveratrol, a natural polyphenol, is an effective antioxidant agent against particulate matter (PM)-induced injuries. The current study was designed to investigate whether resveratrol can regulate autophagy in the process of PM2.5-mediated pulmonary oxidative injury. In the mice model of PM2.5 exposure, we found that PM2.5 increased the contents of malondialdehyde (MDA) and nitric oxide (NO) while decreased the expression of nuclear factor erythroid-2-related factor 2 in the lungs. The levels of 8-hydroxydeoxyguanosine and inflammatory cytokines were increased following PM2.5 exposure. Histological analysis of the lungs revealed inflammatory change in PM2.5 group. Meanwhile, PM2.5 triggered autophagy, as evidenced by the elevated expression of microtubule-associated proteins light chain 3II, Beclin1 and p62. Transmission electron microscopy images showed that autophagosomes accumulated in the lungs after PM2.5 exposure. Furthermore, resveratrol intervention suppressed autophagy and attenuated the oxidative injury resulting from PM2.5 exposure. Our findings provided a valuable insight into the underlying mechanism for the protective effects of resveratrol against PM2.5-induced lung injury, which involves suppression of the autophagic process.

Phenethyl isothiocyanate inhibits colorectal cancer stem cells by suppressing Wnt/ß-catenin pathway.

Cancer stem cells (CSCs) are considered to play essential roles in the process of origination, proliferation, migration, and invasion of cancer, and their properties are regulated by Wnt/ß-catenin pathway. Phenethyl isothiocyanate (PEITC) is a natural product obtained from cruciferous vegetables with anticancer activities. The present study aimed to investigate the inhibitory effect and the underlying mechanisms of PEITC on colorectal CSCs. In this study, we found that PEITC can significantly reduce the size and number of colorectal cancer cell spheroids in serum-free medium. With increasing PEITC concentrations (10-40 µM), the number of spheroids was reduced to about 10% of the control group, and the percentage of CD133+ cells was decreased by about 3-16 folds. PEITC also decreased the expression of CSC markers. Meanwhile, inhibition of proliferation as well as induction of apoptosis of colorectal CSCs was observed after PEITC treatment. Furthermore, through activating Wnt/ß-catenin pathway with LiCl, the inhibitory effects of PEITC on colorectal CSCs were diminished. Our data suggested that PEITC can be an effective inhibitor of colorectal CSCs by targeting Wnt/ß-catenin pathway.

Wnt/ß-catenin pathway mediates (-)-Epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells.

Cancer stem cells (CSCs) play essential role in the progression of many tumors. Wnt/ß-catenin pathway is crucial in maintaining the stemness of CSCs. (-)-Epigallocatechin-3-gallate (EGCG), the major bioactive component in green tea, has been shown to possess anti-cancer activity. To date, the interventional effect of EGCG on lung CSCs has not been elucidated yet. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We revealed that Wnt/ß-catenin pathway was activated in lung CSCs, and downregulation of ß-catenin, abolished lung CSCs traits. Our study further illustrated that EGCG effectively diminished lung CSCs activity by inhibiting tumorsphere formation, decreasing lung CSCs markers, suppressing proliferation and inducing apoptosis. Moreover, We showed that EGCG downregulated Wnt/ß-catenin activation, while upregulation of Wnt/ß-catenin dampened the inhibitory effects of EGCG on lung CSCs. Taken together, these results demonstrated the role of Wnt/ß-catenin pathway in regulating lung CSCs traits and EGCG intervention of lung CSCs. Findings from this study could provide new insights into the molecular mechanisms of lung CSCs intervention.

Effects of Curcumin on Tobacco Smoke-induced Hepatic MAPK Pathway Activation and Epithelial-Mesenchymal Transition In Vivo.

Tobacco smoke is a major risk factor for hepatic cancer. Epithelial-mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice. Our results indicated that exposure of mice to tobacco smoke for 12 weeks led to activation of ERK1/2, JNK, p38 and ERK5 pathways as well as activator protein-1 (AP-1) proteins in liver tissue. Exposure of mice to tobacco smoke reduced the hepatic mRNA and protein expression of the epithelial markers, while the hepatic mRNA and protein levels of the mesenchymal markers were increased. Treatment of curcumin effectively attenuated tobacco smoke-induced activation of ERK1/2 and JNK MAPK pathways, AP-1 proteins and EMT alterations in the mice liver. Our data suggested the protective effect of curcumin in tobacco smoke-triggered MAPK pathway activation and EMT in the liver of BALB/c mice, thus providing new insights into the chemoprevention of tobacco smoke-associated hepatic cancer. Copyright © 2017 John Wiley & Sons, Ltd.

Curcumin Suppresses Lung Cancer Stem Cells via Inhibiting Wnt/ß-catenin and Sonic Hedgehog Pathways.

Cancer stem cells (CSCs) are highly implicated in the progression of human cancers. Thus, targeting CSCs may be a promising strategy for cancer therapy. Wnt/ß-catenin and Sonic Hedgehog pathways play an important regulatory role in maintaining CSC characteristics. Natural compounds, such as curcumin, possess chemopreventive properties. However, the interventional effect of curcumin on lung CSCs has not been clarified. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We showed that the levels of lung CSC markers (CD133, CD44, ALDHA1, Nanog and Oct4) and the number of CD133-positive cells were significantly elevated in the sphere-forming cells. We further illustrated that curcumin efficiently abolished lung CSC traits, as evidenced by reduced tumorsphere formation, reduced number of CD133-positive cells, decreased expression levels of lung CSC markers, as well as proliferation inhibition and apoptosis induction. Moreover, we demonstrated that curcumin suppressed the activation of both Wnt/ß-catenin and Sonic Hedgehog pathways. Taken together, our data suggested that curcumin exhibited its interventional effect on lung CSCs via inhibition of Wnt/ß-catenin and Sonic Hedgehog pathways. These novel findings could provide new insights into the potential therapeutic application of curcumin in lung CSC elimination and cancer intervention. Copyright © 2017 John Wiley & Sons, Ltd.