Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yang; Li, Yueqi; Liu, Jianwen; Ni, Lei

doi:10.1016/j.bbrc.2014.05.110

Cited by 43 publications

(28 citation statements)

References 28 publications

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“…Repeated silica gel and reverse phase column chromatography of the CHCl 3 fraction afforded three new sesquiterpenoids (1-3) and eleven known ones (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The chemical structures of the known compounds were determined to be atractylenolide II (4), 12) atractylenolide III (5), 13) asterolid (6), 14) 8β-methoxyatractylenolide (7), 15) atractylenolide V (8), 16) atractylenolide I (9), 17) atractylenolactam (10), 5) Z-methyl caffeate (11), 18) ferulic acid (12), 19) Z-5-hydroxy ferulic acid (13), 20) and 2-hydroxy ferulic acid (14) 21) based on an analysis of the 1 H-and 13 C-NMR spectra and confirmed by a comparison with those reported in the literature (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Although it has been used as an important herbal medicine for the treatment of hypofunction of the spleen with the loss of appetite, abdominal distension, diarrhea, dizziness, and palpitation due to the retention of phlegm and fluid, edema, spontaneous sweating, and threatened abortion for thousands of years, 2) its active compounds have not been characterized fully. Previous phytochemical investigations of A. macrocephala revealed the presence of polyacetylenes, 3) polysaccharides, 4) sesquiterpenoids, 5) phenylpropanoids, and coumarins 6) with several pharmacological functions, such as the antiinflammatory 7) and inhibitory effects on the proliferation of cultured human tumor cells, 8) aromatase activity 9) and modulatory activity on the γ-aminobutyric acid type A receptor. 10) The atractylodes rhizome is one of the main active components of some Korean folk prescriptions, such as "Guibitang" and "Bojungikgitang," which have been used to enhance of the deficiency of vital energy and synergistic effects.…”

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confidence: 99%

“…11) This study examines whether new metabolites also contribute to the biological activity of A. macrocephala. Three new eudesmane-type sesquiterpenoids, i.e., 13-hydroxylatractylenolide II (1), 4-ketone-atractylenolide III (2) and eudesm-4(15)-ene-7β,11-diol (3), together with eleven known compounds (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were isolated. Their structures were elucidated by combination analysis based on their NMR and mass spectra.…”

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Inflammatory Inhibitory Activity of Sesquiterpenoids from <i>Atractylodes macrocephala</i> Rhizomes

et al. 2016

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Three new sesquiterpenoids, 13-hydroxyl-atractylenolide II (1), 4-ketone-atractylenolide III (2), and eudesm-4(15)-ene-7β,11-diol (3), along with eleven known compounds (4-14), were isolated from the rhizomes of Atractylodes macrocephala. The structures and relative configurations of 1-3 were determined by analysis of the spectroscopic data, and the absolute configurations of 1 and 2 were assigned by circular dichroism technique. The anti-inflammatory activities of these isolates were evaluated against lipopolysaccharideinduced nitric oxide production in macrophage RAW264.7 cells; compounds 4, 7, and 8 exhibited moderate efficacy with IC 50 values of 48.6 0.5, 46.4 3.2, and 32.3 2.9 µM, respectively.

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Section: Resultsmentioning

confidence: 99%

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Inflammatory Inhibitory Activity of Sesquiterpenoids from <i>Atractylodes macrocephala</i> Rhizomes

et al. 2016

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“…After washing twice in cold PBS, staining for stem cell markers or CD47 was performed as described previously (25). Samples were then analyzed by FACScan (BD Bioscience) to detect cell surface CD133, CD44, CD34, and CD47.…”

Section: Methodsmentioning

confidence: 99%

Photodynamic Therapy-mediated Cancer Vaccination Enhances Stem-like Phenotype and Immune Escape, Which Can Be Blocked by Thrombospondin-1 Signaling through CD47 Receptor Protein

Zheng¹,

Zou²,

Wang³

et al. 2015

Journal of Biological Chemistry

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Background: Photodynamic therapy (PDT)-mediated vaccination has shown poor clinical outcomes in tumor treatment. Results: Tumor cells that escaped from PDT-mediated vaccination exhibited enhanced stem-like phenotypes and undermined immunogenicity, which were prevented by interfering TSP-1/CD47/SIRP-␣ signal axis. Conclusion: TSP-1/CD47/SIRP-␣ signal axis is associated with the malignant evolution of tumor cells upon tumor vaccination. Significance: This study provides new evidence for improving the clinical outcome of immunotherapy.

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“…It shows a wide spectrum of pharmacological functions such as anti-inflammatory, antioxidant, and anti-tumor effects on various cell types including cancer cells [6][7][8][9][10]. One study showed that AT-I potently inhibited proliferation and induced apoptosis through inactivating the notch pathway in gastric cancer cells [11]. Another report found that ATL-I significantly sensitized the response of ovarian carcinoma cells to paclitaxel by reducing the protein expression of IL-6, vascular endothelial growth factor (VEGF), and survivin, thus enhancing apoptosis and cell growth inhibition.…”

Section: Introductionmentioning

confidence: 99%

Repression of PDK1- and LncRNA HOTAIR-Mediated EZH2 Gene Expression Contributes to the Enhancement of Atractylenolide 1 and Erlotinib in the Inhibition of Human Lung Cancer Cells

Xiao

Zheng

Tang

et al. 2018

Cell Physiol Biochem

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Background/Aims: We previously showed that the major bioactive compound of Atractylodes macrocephula Koidz atractylenolide 1 (ATL-1) inhibited human lung cancer cell growth by suppressing the gene expression of 3-Phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1). However, the potentially associated molecules and downstream effectors of PDK1 underlying this inhibition, particularly the mechanism for enhancing the anti-tumor effects of epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs), remain unknown. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Western blot analyses were performed to examine the protein expressions of PDK1 and of zeste homolog 2 (EZH2). The levels of long non-coding RNA (lncRNA) and HOX transcript antisense RNA (HOTAIR) were examined via qRT-PCR. RNA-binding protein immunoprecipitation assays were used to analyze HOTAIR interaction with EZH2. The promoter activity of the EZH2 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expressions of PDK1, HOTAIR, and EZH2 were conducted via transient transfection assays. A xenografted tumor model was used to further evaluate the effect of ATL-1 in the presence or absence of erlotinib in vivo. Results: We showed that the combination of ATL-1 and EGFR-TKI erlotinib further inhibited growth and induced cell arrest of the human lung cancer cells, determined by both MTT and flow cytometry assays. ATL-1 inhibited the protein expression and the promoter activity of EZH2, which was reversed in cells with PDK1 overexpression. Interestingly, ATL-1 inhibited the expression levels of HOTAIR. While silencing HOTAIR inhibited the expressions of PDK1 and EZH2, overexpression of HOTAIR reduced the ATL-1-reduced PDK1 and EZH2 protein expressions and EZH2 promoter activity. In addition, ATL-1 reduced the HOTAIR binding to the EZH2 protein. Moreover, we found that exogenously expressed EZH2 antagonized the effect of ATL-1 on cell growth inhibition. Consistent with the in vitro results, ATL-1 inhibited tumor growth and the expression levels of HOTAIR, protein expressions of EZH2 and PDK1 in vivo. Importantly, there was synergy of the combination of ATL-1 and erlotinib in this process. Conclusion: Here, we provide the first evidence that ATL-1 inhibits lung cancer cell growth through inhibiting not only the PDK1 but also the lncRNA HOTAIR, which results in the reduction of one downstream effector EZH2 expression. The novel interplay between the HOTAIR and EZH2, as well as repressions of the PDK1 and HOTAIR coordinate the overall effects of ATL-1. Importantly, the combination of ATL-1 and EGFR-TKI erlotinib exhibits synergy. Thus, targeting the PDK1- and HOTAIR-mediated downstream molecule EZH2 by the combination of ATL-1 and erlotinib potentially facilitates the development of an additional novel strategy to combat lung cancer.

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Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

Cited by 43 publications

References 28 publications

Inflammatory Inhibitory Activity of Sesquiterpenoids from <i>Atractylodes macrocephala</i> Rhizomes

Inflammatory Inhibitory Activity of Sesquiterpenoids from <i>Atractylodes macrocephala</i> Rhizomes

Photodynamic Therapy-mediated Cancer Vaccination Enhances Stem-like Phenotype and Immune Escape, Which Can Be Blocked by Thrombospondin-1 Signaling through CD47 Receptor Protein

Repression of PDK1- and LncRNA HOTAIR-Mediated EZH2 Gene Expression Contributes to the Enhancement of Atractylenolide 1 and Erlotinib in the Inhibition of Human Lung Cancer Cells

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