Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway.

Abstract:

:Cucurbitacin D (CuD), isolated from plants from the Cucurbitaceae family, is a potential antitumour agent since it inhibits proliferation, migration and metastasis of cancer cells. Despite CuD antitumour activity in cancer cells, the effects of CuD on gastric cancer cell lines remain unclear. The present study aimed to investigate the effects of CuD on gastric cancer cell growth and death. Human gastric cancer cell lines (AGS, SNU1 and Hs746T) were cultured and treated with different concentrations of CuD (0, 0.25, 0.5, 1 and 2 µM). Cell proliferation was assessed using Cell Counting Kit‑8 assay. Oxidative stress was evaluated by generation of reactive oxygen species (ROS). Cell apoptosis was assessed by terminal deoxynucleotidyl transferase 2'‑deoxyuridine‑5'‑triphosphate nick‑end labelling (TUNEL) staining. Levels of intracellular Ca2+ and adenosine triphosphate (ATP) were also assessed. In the present study, CuD effectively inhibited cell proliferation, triggered ROS generation and induced apoptosis in gastric cancer cells (AGS, SNU1 and Hs746T). Treatment with CuD increased intracellular Ca2+ and ATP levels. CuD also stimulated the expression of inducible nitric oxide synthase (iNOS), which augmented nitric oxide production. In addition, CuD activated the mitochondrial apoptosis pathway, which increased the expression of Bax and the release of cleaved caspace‑9 (C‑caspase‑9) and cytochrome c, decreased the expression of B‑cell lymphoma 2 (Bcl‑2). The mechanism of action of CuD involved the regulation of the protein kinase B/mechanistic target of rapamycin (Akt/mTOR) pathway. We confirmed the effects of CuD on gastric tumours via an in vivo xenograft gastric tumour model. In conclusion, CuD inhibited Akt and activated the iNOS pathway, leading to higher ROS and nitric oxide production, which accelerated gastric cancer cell apoptosis.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Zhang YZ,Wang CF,Zhang LF

doi

10.3892/or.2018.6361

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

2595-2603

issue

6

eissn

1021-335X

issn

1791-2431

journal_volume

39

pub_type

杂志文章
  • Potential for molecular targeted therapy of HER-2/neu for invasive bladder cancer: examination of gene amplification by fluorescence in situ hybridization.

    abstract::Analysis of HER-2/neu gene amplification by fluorescence in situ hybridization was performed in 40 patients with invasive bladder cancer in order to evaluate the potential for molecular targeted therapy of HER-2 as a tailor-made treatment for patients with invasive bladder cancer. This study included 40 patients seen ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Yamada Y,Naruse K,Nakamura K,Aoki S,Taki T,Tobiume M,Zennami K,Katsuda R,Hirano M,Hayashida K,Mizumukai E,Nanaura H,Honda N

    更新日期:2007-11-01 00:00:00

  • Two-dimensional differential in-gel electrophoresis for identification of gastric cancer-specific protein markers.

    abstract::Gastric cancer is the second most common fatal malignancy in the world. Proteomics studies of clinical tumor samples have led to the identification of specific protein markers of gastric cancer detection and better understanding the carcinogenesis of gastric cancer. Gastric cancer tissue of epithelial origin and adjac...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000371

    authors: Wu C,Luo Z,Chen X,Wu C,Yao D,Zhao P,Liu L,Shi B,Zhu L

    更新日期:2009-06-01 00:00:00

  • β‑carotene reverses tobacco smoke‑induced gastric EMT via Notch pathway in vivo.

    abstract::Tobacco smoke is one of the serious risk factors of gastric cancer. Epithelial‑mesenchymal transition (EMT) has been shown to be associated with the initiation and carcinogenesis of gastric cancer. The role of Notch pathway in regulating tobacco smoke-induced EMT has not been investigated. β‑carotene, a carotenoid pre...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6246

    authors: Lu L,Chen J,Li M,Tang L,Wu R,Jin L,Liang Z

    更新日期:2018-04-01 00:00:00

  • Gentian violet inhibits MDA-MB-231 human breast cancer cell proliferation, and reverses the stimulation of osteoclastogenesis and suppression of osteoblast activity induced by cancer cells.

    abstract::Gentian violet (GV) is a cationic triphenylmethane dye, with potent antifungal and antibacterial activity. We recently reported that in vitro GV suppresses the differentiation of bone resorbing osteoclasts while stimulating the differentiation and activity of bone forming osteoblasts. Breast cancer is highly metastati...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4190

    authors: Yamaguchi M,Vikulina T,Weitzmann MN

    更新日期:2015-10-01 00:00:00

  • Topical vidarabine or 5-fluorouracil treatment against persistent HPV in genital (pre)cancerous lesions.

    abstract::In the present study, effectiveness of topical vidarabine or subsequent 5-fluorouracil (5-FU) administration was examined against persistent genital human papillomavirus (HPV) infection after local surgery. Thirty patients underwent local eradication treatment of uterine cervical intra-epithelial neoplasia (CIN) and s...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Niwa K,Tagami K,Lian Z,Gao J,Mori H,Tamaya T

    更新日期:2003-09-01 00:00:00

  • BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis.

    abstract::BTG1, which belongs to the BTG/Tob family, regulates cell cycle progression in a variety of cell types and appears to play roles in inhibiting proliferation, promoting apoptosis and stimulating cellular differentiation in multiple cell types. However, it remains unclear whether BTG1 is a breast cancer suppressor gene,...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2697

    authors: Zhu R,Zou ST,Wan JM,Li W,Li XL,Zhu W

    更新日期:2013-11-01 00:00:00

  • Effect of bone marrow mesenchymal stem cells from blastic phase chronic myelogenous leukemia on the growth and apoptosis of leukemia cells.

    abstract::Chronic myelogenous leukemia (CML) has a typical progressive course with transition from a chronic phase to a terminal blast crisis phase. However, the mechanisms that lead to disease progression remain unclear. Bone marrow mesenchymal stem cells (BMMSCs) play important roles in maintaining the bone marrow microenviro...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2518

    authors: Han Y,Wang Y,Xu Z,Li J,Yang J,Li Y,Shang Y,Luo J

    更新日期:2013-08-01 00:00:00

  • Circulating levels of angiogenesis-related growth factors in breast cancer: A study to profile proteins responsible for tubule formation.

    abstract::The present study exploited a versatile in vitro endothelial cell/fibroblast co-culture cell system to investigate the association between angiogenesis and breast cancer by comparing the capacity of plasma from women with breast cancer and age-matched controls, to influence tubule formation and modulate angiogenesis i...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5803

    authors: Barron GA,Goua M,Wahle KWJ,Bermano G

    更新日期:2017-09-01 00:00:00

  • Trastuzumab and docetaxel in a preclinical organotypic breast cancer model using tissue slices from mammary fat pad: Translational relevance.

    abstract::With the ever-increasing number of drugs approved to treat cancers, selection of the optimal treatment regimen for an individual patient is challenging. Breast cancer complexity requires novel predictive methods and tools. In the present study, we set up experimental conditions to obtain an 'ex vivo' organotypic cultu...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4074

    authors: Vesci L,Carollo V,Roscilli G,Aurisicchio L,Ferrara FF,Spagnoli L,De Santis R

    更新日期:2015-09-01 00:00:00

  • Involvement of TMEM22 overexpression in the growth of renal cell carcinoma cells.

    abstract::In order to clarify the molecular mechanism involved in renal carcinogenesis, and to identify molecular targets for development of novel treatments of renal cell carcinoma (RCC), we previously analyzed genome-wide gene expression profiles of clear-cell types of RCC by cDNA microarray. Among the transcativated genes, w...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Dobashi S,Katagiri T,Hirota E,Ashida S,Daigo Y,Shuin T,Fujioka T,Miki T,Nakamura Y

    更新日期:2009-02-01 00:00:00

  • A single nucleotide polymorphism in fibronectin 1 determines tumor shape in colorectal cancer.

    abstract::Depressed and flat surface lesions are not easy to identify with routine colonoscopies during screening for colorectal cancer (CRC). Identifying clinically relevant genes that influence tumor shape could be useful when screening for the presence of depressed lesions. Total RNA was extracted from tumor cells collected ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3251

    authors: Kida H,Takano Y,Yamamoto K,Mori M,Yanaga K,Tanaka J,Kudo SE,Mimori K

    更新日期:2014-08-01 00:00:00

  • Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway.

    abstract::Breast cancer which is the most common type of diagnosed cancer among women worldwide possesses metastatic potential, multi‑drug resistance, and high mortality. The NF‑κB signaling pathway has been revealed to be abnormally activated in breast cancer cells and closely associated with high metastasis and poor prognosis...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7891

    authors: Zeng A,Liang X,Zhu S,Liu C,Wang S,Zhang Q,Zhao J,Song L

    更新日期:2020-12-09 00:00:00

  • Alteration of gene expression and DNA methylation in drug-resistant gastric cancer.

    abstract::The mechanisms of drug resistance in cancer are not fully elucidated. To study the drug resistance of gastric cancer, we analyzed gene expression and DNA methylation profiles of 5-fluorouracil (5-FU)- and cisplatin (CDDP)-resistant gastric cancer cells and biopsy specimens. Drug-resistant gastric cancer cells were est...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3014

    authors: Maeda O,Ando T,Ohmiya N,Ishiguro K,Watanabe O,Miyahara R,Hibi Y,Nagai T,Yamada K,Goto H

    更新日期:2014-04-01 00:00:00

  • Immunohistochemical study of chymase-positive mast cells in inflammatory bowel disease.

    abstract::Mast cell-derived chymase promotes inflammatory responses and tissue fibrosis. Although previous studies have reported changes in the number of mucosal mast cells in inflammatory bowel disease (IBD), the behaviour of chymase immunopositive mast cells has not been studied. In this study, we immunohistochemically invest...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Andoh A,Deguchi Y,Inatomi O,Yagi Y,Bamba S,Tsujikawa T,Fujiyama Y

    更新日期:2006-07-01 00:00:00

  • The effects of the Wnt/β‑catenin signaling pathway on apoptosis in HeLa cells induced by carbon ion irradiation.

    abstract::The molecular mechanisms underlying the biological effects of carbon ions are unclear. The aim of this study was to explore the Wnt/β‑catenin pathway in regulating carbon ion (12C6+) radiation‑induced cellular toxicity. HLY78 is a Wnt‑specific small molecular modulator, whose effects on 12C6+ radiation‑induced damage ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7581

    authors: Si J,Zhang J,Gan L,Guo M,Xie Y,Di C,Sun C,Wang F,Yan J,Zhang H

    更新日期:2020-07-01 00:00:00

  • Clinical factors in prediction of prognosis after anterior resection with total mesorectal excision for carcinoma of the rectum.

    abstract::The aim of the study was to estimate the long-term results and the prognostic value of clinical and pathological factors following R0 anterior resection with total mesorectal excision (TME). Ninety-eight consecutive patients with histologically confirmed rectal cancer were studied prospectively with five-year follow-u...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Szynglarewicz B,Matkowski R,Forgacz J,Pudelko M,Smorag Z,Dryl J,Kornafel J

    更新日期:2007-02-01 00:00:00

  • Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation.

    abstract::Garlic and its constituents are reported to have a preventive effect against colorectal cancer in animal models. Aged garlic extract (AGE), which is produced by natural extraction from fresh garlic for more than 10 months in aqueous ethanol, also has reputed chemopreventive effects on colon carcinogenesis, but has nev...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3705

    authors: Jikihara H,Qi G,Nozoe K,Hirokawa M,Sato H,Sugihara Y,Shimamoto F

    更新日期:2015-03-01 00:00:00

  • Malignant transformation of host stromal fibroblasts derived from the bone marrow traced in a dual-color fluorescence xenograft tumor model.

    abstract::Solid tumors are abnormal tissues containing tumor and non-tumor cells, also known as tumor stromal cells. However, the malignant potential of tumor stromal cells remains largely unknown. The aim of the present study was to investigate the malignant potential of host bone marrow‑derived stroma cells in transplanted su...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4281

    authors: Dai X,Chen H,Chen Y,Wu J,Wang H,Shi J,Fei X,Wang Z,Wang A,Dong J,Lan Q,Huang Q

    更新日期:2015-12-01 00:00:00

  • NSPc1 polycomb protein complex binds and cross‑talks to lncRNAs in glioma H4 cells.

    abstract::Recently, emerging evidence shows that a number of long non‑coding RNAs (lncRNAs) recruit polycomb group (PcG) proteins to specific chromatin loci to silence relevant gene expression. In the present study, we provided evidence that lncRNA candidates, selected by bioinformatic analysis and nervous system polycomb 1 (NS...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7000

    authors: Wang Y,Liang Z,Li H,Tao J,Sun Y,Gong Y

    更新日期:2019-04-01 00:00:00

  • microRNA-21 modulates cell proliferation and sensitivity to doxorubicin in bladder cancer cells.

    abstract::Transitional cell carcinomas (TCCs) of the urinary bladder are common malignancies with a high recurrence rate. Since microRNA-21 (miR-21) may contribute to tumorigenesis and chemoresistance in many cancer types, we aimed to investigate its efficacy in TCCs. The expression of miR-21 and its target PTEN was determined ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1245

    authors: Tao J,Lu Q,Wu D,Li P,Xu B,Qing W,Wang M,Zhang Z,Zhang W

    更新日期:2011-06-01 00:00:00

  • Induction of eEF2-specific antitumor CTL responses in vivo by vaccination with eEF2-derived 9mer-peptides.

    abstract::Eukaryotic elongation factor 2 (eEF2) is an essential factor for protein synthesis. Previous studies have shown that the eEF2 gene was overexpressed and plays an oncogenic role in various types of cancers and that eEF2 gene product elicited both humoral immune responses to produce eEF2-specific IgG autoantibody in can...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4589

    authors: Nakajima H,Murakami Y,Morii E,Akao T,Tatsumi N,Odajima S,Fukuda M,Machitani T,Iwai M,Kawata S,Hojo N,Oka Y,Sugiyama H,Oji Y

    更新日期:2016-04-01 00:00:00

  • Efficacy of the combined use of bevacizumab and irinotecan as a postoperative adjuvant chemotherapy in colon carcinoma.

    abstract::We evaluated the efficacy of anti-human VEGF antibody (bevacizumab) with or without irinotecan (CPT-11) against lung metastases in which neovascularization was already induced, as a postoperative adjuvant therapy using orthotopically implanted colon cancer in rat. The high VEGF productive KM12SM human colon cancer cel...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Mizobe T,Ogata Y,Murakami H,Akagi Y,Ishibashi N,Mori S,Sasatomi T,Shirouzu K

    更新日期:2008-09-01 00:00:00

  • STMN1, a prognostic predictor of esophageal squamous cell carcinoma, is a marker of the activation of the PI3K pathway.

    abstract::The esophageal squamous cell carcinoma (ESCC) subtype with STMN1 overexpression has a high likelihood of lymphatic metastatic recurrence. However, the underlying mechanism remains to be further elucidated. We assessed the expression level of STMN1 and PTEN in 96 pN0 ESCC patient tissues using immunohistochemistry and ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.6145

    authors: Jiang W,Huang S,Song L,Wang Z

    更新日期:2018-02-01 00:00:00

  • Establishment and characterization of a human adenoid cystic carcinoma cell line forming colonies cultured in collagen gel and transplantable in nude mice.

    abstract::We established a new cell line (ACCNS) from human adenoid cystic carcinoma (AdCC) of the maxilla, using tissue culture techniques and it has been successfully subcultured for more than 100 passages during 2 years. The population doubling time was approximately 39.2 h on a plastic dish. In type I collagen gel culture, ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Tanaka N,Urabe K,Hashitani S,Sakurai K,Urade M

    更新日期:2007-02-01 00:00:00

  • Atorvastatin partially inhibits the epithelial-mesenchymal transition in A549 cells induced by TGF-β1 by attenuating the upregulation of SphK1.

    abstract::Statins are the most effective drugs used in the reduction of intracellular synthesis of cholesterol. Numerous studies have confirmed that statins reduce the risk of multiple types of cancers. Statin use in cancer patients is associated with reduced cancer-related mortality. Epithelial-to-mesenchymal transition (EMT),...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4897

    authors: Fan Z,Jiang H,Wang Z,Qu J

    更新日期:2016-08-01 00:00:00

  • Pharmacological inhibition of Rho-kinase signaling with Y-27632 blocks melanoma tumor growth.

    abstract::Primarily through in vitro studies, the Rho-family of small GTPases and their effector proteins have been implicated in mediating oncogenic properties of cancer cells. We sought to determine if pharmacological inhibition of the RhoA effector proteins known as Rho-kinases (ROCK) with the small molecule inhibitor Y-2763...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Routhier A,Astuccio M,Lahey D,Monfredo N,Johnson A,Callahan W,Partington A,Fellows K,Ouellette L,Zhidro S,Goodrow C,Smith A,Sullivan K,Simone P,Le L,Vezuli B,Zohni M,West E,Gleason D,Bryan B

    更新日期:2010-03-01 00:00:00

  • Caudatin inhibits human hepatoma cell growth and metastasis through modulation of the Wnt/β-catenin pathway.

    abstract::In the present study, we investigated the antitumor activity of caudatin in the human hepatoma cell line SMMC‑7721 by analysis of cell viability, cell cycle distribution, apoptosis and metastasis. The results showed that caudatin impaired the cell viability and inhibited the growth of SMMC-7721 cells in a time- and do...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2749

    authors: Luo Y,Sun Z,Li Y,Liu L,Cai X,Li Z

    更新日期:2013-12-01 00:00:00

  • Overexpression of WNT5B promotes COLO 205 cell migration and invasion through the JNK signaling pathway.

    abstract::WNT5B is a member of the WNT family that has been reported to be overexpressed in a variety of cancer cell lines and tissues, including colorectal cancer (CRC). However, the potential roles of WNT5B in tumorigenesis have not been reported. In the present study, the WNT5B gene was transfected into CRC cells and generat...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4772

    authors: Zhang Y,Lin L,Jin Y,Lin Y,Cao Y,Zheng C

    更新日期:2016-07-01 00:00:00

  • Identification of novel therapeutic targets in the secretome of ionizing radiation‑induced senescent tumor cells.

    abstract::Cellular senescence is a state of irreversible growth arrest that can be triggered by multiple mechanisms, including telomere shortening, the epigenetic derepression of the INK4α/ARF locus and DNA damage. Senescence has been considered a tumor‑suppressing mechanism that permanently arrests cells at risk for malignant ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4473

    authors: Hwang HJ,Jung SH,Lee HC,Han NK,Bae IH,Lee M,Han YH,Kang YS,Lee SJ,Park HJ,Ko YG,Lee JS

    更新日期:2016-02-01 00:00:00

  • Histone deacetylase inhibitors and aspirin interact synergistically to induce cell death in ovarian cancer cells.

    abstract::Histone deacetylase inhibitors (HDIs) as well as non-steroidal anti-inflammatory drugs including aspirin show promise as antineoplastic agents. The treatment with both HDIs and aspirin can result in hyperacetylation of proteins. In this study, we investigated whether HDIs and aspirin interacted in inducing anticancer ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Sonnemann J,Hüls I,Sigler M,Palani CD,Hong le TT,Völker U,Kroemer HK,Beck JF

    更新日期:2008-07-01 00:00:00