Evaluation of chemotherapeutic and cancer-protective properties of sphingosine and C2-ceramide in a human breast stem cell derived carcinogenesis model.

Abstract:

:The overall goal of the present study was to evaluate the chemotherapeutic and cancer‑protective properties of D‑erythro‑sphingosine (sphingosine) and C2‑ceramide using a human breast epithelial cell (HBEC) culture system, which represents multiple‑stages of breast carcinogenesis. The HBEC model includes Type I HBECs (normal stem), Type II HBECs (normal differentiated) and transformed cells (immortal/non‑tumorigenic cells and tumorigenic cells, which are transformed from the same parental normal stem cells). The results of the present study indicate that sphingosine preferentially inhibits proliferation and causes death of normal stem cells (Type I), tumorigenic cells, and MCF7 breast cancer cells, but not normal differentiated cells (Type II). In contrast to the selective anti‑proliferative effects of sphingosine, C2‑ceramide inhibits proliferation of normal differentiated cells as well as normal stem cells, tumorigenic cells, and MCF7 cancer cells with similar potency. Both sphingosine and C2‑ceramide induce apoptosis in tumorigenic cells. Among the sphingosine stereoisomers (D‑erythro, D‑threo, L‑erythro, and L‑threo) and sphinganine that were tested, L‑erythro‑sphingosine most potently inhibits proliferation of tumorigenic cells. The inhibition of breast tumorigenic/cancer cell proliferation by sphingosine was accompanied by inhibition of telomerase activity. Sphingosine at non‑cytotoxic concentrations, but not C2‑ceramide, induces differentiation of normal stem cells (Type I), thereby reducing the number of stem cells that are more susceptible to neoplastic transformation. To the best of our knowledge, the present study demonstrates one of the first results that sphingosine can be a potential chemotherapeutic and cancer‑protective agent, whereas C2‑ceramide is not an ideal chemotherapeutic and cancer‑protective agent due to its anti‑proliferative effects on Type II HBECs and its inability to induce the differentiation of Type I to Type II HBECs.

journal_name

Int J Oncol

authors

Ahn EH,Yang H,Hsieh CY,Sun W,Chang CC,Schroeder JJ

doi

10.3892/ijo.2018.4641

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

655-664

issue

2

eissn

1019-6439

issn

1791-2423

journal_volume

54

pub_type

杂志文章
  • NRG1 regulates redox homeostasis via NRF2 in papillary thyroid cancer.

    abstract::Thyroid cancer is a common endocrine cancer, of which papillary thyroid cancer (PTC) is the most common type. Neuregulin 1 (NRG1), a glycoprotein mediating cell‑cell signaling, plays vital roles in cellular activities; however, its role in PTC progression remains poorly understood. In this study, we performed immunohi...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4426

    authors: Zhang TT,Qu N,Sun GH,Zhang L,Wang YJ,Mu XM,Wei WJ,Wang YL,Wang Y,Ji QH,Zhu YX,Shi RL

    更新日期:2018-08-01 00:00:00

  • Correlation between the immunohistochemical and mRNA expression of glutathione S-transferase-pi and cisplatin plus etoposide chemotherapy response in patients with untreated primary non-small cell lung cancer.

    abstract::Patients who have inoperable lung cancer usually undergo chemotherapy and have problems such as a resistance against chemotherapeutic agents during the treatment. Glutathione S-transferase (GST) is one of the detoxication-related enzymes. We studied the relationship between immunohisto-chemical staining of GST-pi type...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.11.1.127

    authors: Arai T,Yasuda Y,Takaya T,Yoshimi N,Ito H,Fujiwara H

    更新日期:1997-07-01 00:00:00

  • In vivo induction of dendritic cell-mediated cytotoxicity against allogeneic pancreatic carcinoma cells.

    abstract::The objective of this study was to assess the toxicity and immunological response induced by autologous dendritic cells (DCs) pulsed with allogeneic tumor lysate in a pancreatic cancer patient. The lack of available tumor peptides in pancreatic cancer strongly supports the idea to use allogeneic tumor cells as a sourc...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Stift A,Friedl J,Dubsky P,Bachleitner-Hofmann T,Benkoe T,Brostjan C,Jakesz R,Gnant M

    更新日期:2003-03-01 00:00:00

  • Vandetanib alters the protein pattern in malignant glioma and normal brain in the BT4C rat glioma model.

    abstract::The treatment of glioblastoma is unsatisfactory. Improved understanding of the biological effects of treatment, together with development of new tools to predict outcome of the initiated treatment are therefore of great need. Vandetanib (ZD6474) is mainly a vascular endothelial growth factor (VEGF) and epidermal growt...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000739

    authors: Wibom C,Sandström M,Henriksson R,Antti H,Johansson M,Bergenheim AT

    更新日期:2010-10-01 00:00:00

  • Multiple regions with allelic loss at chromosome 3 in superficial multifocal bladder tumors.

    abstract::We have examined six patients with multiple low grade, low stage superficial multifocal bladder tumors with surrounding tissues for loss of heterozygosity (LOH) and microsatellite instability at chromosome 3, totaling 76 samples. The majority (4/5) of the patients had LOH at or close to the fragile histidine triad (FH...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.18.1.203

    authors: Louhelainen J,Wijkström H,Hemminki K

    更新日期:2001-01-01 00:00:00

  • Protein profiling of osteosarcoma tissue and soft callus unveils activation of the unfolded protein response pathway.

    abstract::Oncogenic drivers of osteosarcoma remain controversial due to the complexity of the genomic background of the disease. There are limited novel therapeutic options, and the survival rate of patients with osteosarcoma has not improved in decades. Genomic instability leads to complexity in various pathways, which is pote...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2019.4737

    authors: Chaiyawat P,Sungngam P,Teeyakasem P,Sirikaew N,Klangjorhor J,Settakorn J,Diskul-Na-Ayudthaya P,Chokchaichamnankit D,Srisomsap C,Svasti J,Pruksakorn D

    更新日期:2019-05-01 00:00:00

  • Hydrogen peroxide overload increases adriamycin-induced apoptosis of SaOS(2)FM, a manganese superoxide dismutase-overexpressing human osteosarcoma cell line.

    abstract::We previously developed a new microscopic observation system that enables time-lapse quantitative analysis of apoptosis and necrosis. With this system we quantitatively analyzed adriamycin (ADR)-induced cell death using manganese superoxide dismutase (MnSOD)- and wild-type p53-gene transfectants on SaOS(2), a p53-defi...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Wang Y,Kuroda M,Gao XS,Asaumi J,Shibuya K,Kawasaki S,Akaki S,St Clair D,Hiraki Y,Kanazawa S

    更新日期:2005-05-01 00:00:00

  • BML-275, an AMPK inhibitor, induces DNA damage, G2/M arrest and apoptosis in human pancreatic cancer cells.

    abstract::Adenosine monophosphate-activated protein kinase (AMPK) is a principal intracellular energy sensor which regulates energy producing pathways and energy requiring pathways when the cellular AMP/ATP ratio is altered. BML-275 (compound C), a well-known inhibitor of AMPK, has been found...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1672

    authors: Duong HQ,Hwang JS,Kim HJ,Seong YS,Bae I

    更新日期:2012-12-01 00:00:00

  • Oncogenic mutation of the p53 gene derived from head and neck cancer prevents cells from undergoing apoptosis after DNA damage.

    abstract::A p53 functional analysis system, which can identify the types of abnormality of p53, such as loss of function, dominant negative function, or gain of oncogenic function, is now required. In this study, we examined the functional diversity of several mutations of p53 derived from human head and neck cancer cells. The ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Kawamata H,Omotehara F,Nakashiro K,Uchida D,Shinagawa Y,Tachibana M,Imai Y,Fujimori T

    更新日期:2007-05-01 00:00:00

  • Induction chemotherapy for breast carcinoma: predictive markers and relation with outcome.

    abstract::Induction chemotherapy provides an excellent model for evaluation of potential predictive factors. We studied expression of SBR grade, estrogen (ER) and progesterone (PR) receptors, HER2, Ki67 and P53 on core biopsies before and after chemotherapy in a series of 115 patients, who received anthracycline-based induction...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Penault-Llorca F,Cayre A,Bouchet Mishellany F,Amat S,Feillel V,Le Bouedec G,Ferrière JP,De Latour M,Chollet P

    更新日期:2003-06-01 00:00:00

  • The flow cytometric nuclear-DNA content, tumor-origin, nuclear size and prognosis in squamous-cell lung-cancer.

    abstract::We examined the relationships among nuclear DNA content, tumor origin, nuclear size, and prognosis in squamous cell lung cancer. Central tumors had significantly higher DNA aneuploidy (83%, p<0.01) and DNA indices (1.65+/-0.40, p<0.01) than did peripheral tumors (40%, 1.29+/-0.37, respectively). All six women in the s...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.1.3.325

    authors: Miyamoto H,Isobe H,Akita H,Ishiguro A,Endo T,Inoue S,Kawakami Y

    更新日期:1992-08-01 00:00:00

  • Identification of a nuclear protein, LRRC42, involved in lung carcinogenesis.

    abstract::On the basis of the gene expression profiles of 120 lung cancer cases using a cDNA microarray containing 27,648 genes or expressed sequence tags (ESTs), we identified LRRC42 (Leucine-rich repeat containing 42) to be significantly upregulated in the majority of lung cancers. Northern blot analysis demonstrated that LRR...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2418

    authors: Fujitomo T,Daigo Y,Matsuda K,Ueda K,Nakamura Y

    更新日期:2014-07-01 00:00:00

  • HIF1-positive and HIF1-negative glioblastoma cells compete in vitro but cooperate in tumor growth in vivo.

    abstract::Glioblastoma multiforme (GBM) is characterized by extensive angiogenesis that is mostly orchestrated by the hypoxia inducible factor HIF-1. Deregulation of HIF-1 is believed to contribute to cancer initiation and progression. However, instances have been described in which loss of HIF-1 leads to more aggressive tumors...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000554

    authors: Fiorenzo P,Mongiardi MP,Dimitri D,Cozzolino M,Ferri A,Montano N,Trevisi G,Maira G,Battistini L,Falchetti ML,Levi A,Pallini R

    更新日期:2010-04-01 00:00:00

  • Hepatic arterial bolus chemotherapy for colorectal metastases using an implantable port.

    abstract::Twenty-one patients with isolated colorectal liver metastases underwent hepatic artery infusion (HAI) port implantation for regional chemotherapy with bolus injections of 5-FU, LV and fast drip of cisplatin. Ten of the 21 patients had previously failed systemic chemotherapy before HAI. Toxicity was moderate and no nee...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.9.6.1295

    authors: Lyass S,Lyass O,Gabizon A,Peretz T,Eid A,Muggiasullam M,Durst A,Shiloni E

    更新日期:1996-12-01 00:00:00

  • Differential modulation of cellular and viral promoters by p73 and p53.

    abstract::p73 has been shown to transcriptionally activate genes positively responsive to wild-type p53. In order to undertake a comparative study of functions of p53 and p73 we have cloned the cDNA of p73 from MCF-7 cells. Adenovirus onco-protein E1A inhibits the transactivation by p73; a deletion mutant of E1A incapable of in...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Deb D,Lanyi A,Scian M,Keiger J,Brown DR,Le Roith D,Deb SP,Deb S

    更新日期:2001-02-01 00:00:00

  • Identification by a Digital Gene Expression Displayer (DGED) and test by RT-PCR analysis of new mRNA candidate markers for colorectal cancer in peripheral blood.

    abstract::Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The presen...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000701

    authors: Lauriola M,Ugolini G,Rosati G,Zanotti S,Montroni I,Manaresi A,Zattoni D,Rivetti S,Mattei G,Coppola D,Strippoli P,Taffurelli M,Solmi R

    更新日期:2010-08-01 00:00:00

  • Suppression of autophagic genes sensitizes CUG2-overexpressing A549 human lung cancer cells to oncolytic vesicular stomatitis virus-induced apoptosis.

    abstract::We showed in our previous study that cancer upregulated gene (CUG) 2, a novel oncogene, confers resistance to infection of oncolytic vesicular stomatitis virus (VSV) by activating Stat1-mediated signal transduction. Since many studies have reported that autophagy is involved in virus replication, we investigated wheth...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2264

    authors: Malilas W,Koh SS,Lee S,Srisuttee R,Cho IR,Moon J,Kaowinn S,Johnston RN,Chung YH

    更新日期:2014-04-01 00:00:00

  • Clinicopathologic study of multiple primary superficial carcinoma of the esophagus.

    abstract::Endoscopic examination with iodine staining has led to the easy detection of multiple superficial esophageal carcinoma (MSEC). The purpose of this study was to better understand the characteristics of MSEC. Of 49 patients with multiple esophageal carcinomas, 19 had superficial carcinoma. Multiple esophageal carcinomas...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.12.2.421

    authors: Fujii T,Yamana H,Fujita H,Sueyoshi S,Nakashima A,Hayashi I,Nishi M,Kato S,Shirouzu K,Morimatsu M

    更新日期:1998-02-01 00:00:00

  • The detection of telomerase activity in patients with adenocarcinoma of the pancreas by fine needle aspiration.

    abstract::Telomerase activation in differentiated cells is associated with cell immortalization. Detection of telomerase expression in cancer provides a potential biomarker to be evaluated in the diagnosis and prognosis of cancer patients. Analysis of telomerase activity in biopsy specimens may serve as a useful marker for the ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.17.2.381

    authors: Pearson AS,Chiao P,Zhang L,Zhang W,Larry L,Katz RL,Evans DB,Abbruzzese JL

    更新日期:2000-08-01 00:00:00

  • Induction of differentiation and tetraploidy by long-term treatment of C6 rat glioma cells with erucylphosphocholine.

    abstract::Induction of differentiation represents a promising concept for chemotherapy of malignant gliomas, which are often refractory even to the combined treatment with surgery, irradiation and chemotherapy. Since anti-neoplastic alkylphosphocholines can induce differentiation of leukemic cell lines, the effects of the intra...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.19.4.673

    authors: Jendrossek V,Kugler W,Erdlenbruch B,Eibl H,Lakomek M

    更新日期:2001-10-01 00:00:00

  • Absence of death receptor translocation into lipid rafts in acquired TRAIL-resistant NSCLC cells.

    abstract::Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a major limitation for its clinical use. The mechanisms of TRAIL resistance have been mostly studied in the context of cell lines that are intrinsically resistant to TRAIL. However, little is known about the molecular alterations that con...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1748

    authors: Ouyang W,Yang C,Zhang S,Liu Y,Yang B,Zhang J,Zhou F,Zhou Y,Xie C

    更新日期:2013-02-01 00:00:00

  • Insitu nick translation, an alternative to cytogenetics in analyzing mutagen effects on human-cells.

    abstract::A chromosomal break indicates a double-stranded DNA break of the chromatin fiber. Cytogenetic observations can enumerate chromosome breaks but cannot detect single-stranded DNA breaks (nicks). When a high frequency of chromosomal breaks occurs in a cell population, whether spontaneously occurred or mutagen induced, a ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2.6.873

    authors: Wang R,Hsu T,Liang J

    更新日期:1993-06-01 00:00:00

  • Mesenchymal stem cells show little tropism for the resting and differentiated cancer stem cell-like glioma cells.

    abstract::Intrinsic resistance of glioma cells to radiation and chemotherapy is currently hypothesized to be partially attributed to the existence of cancer stem cells. Emerging studies suggest that mesenchymal stem cells may serve as a potential carrier for delivery of therapeutic genes to disseminated glioma cells. However, t...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2284

    authors: Liu Z,Jiang Z,Huang J,Huang S,Li Y,Sheng F,Yu S,Yu S,Liu X

    更新日期:2014-04-01 00:00:00

  • Bioinformatic analysis of chemokine (C-C motif) ligand 21 and SPARC-like protein 1 revealing their associations with drug resistance in ovarian cancer.

    abstract::Chemokine (C-C motif) ligand 21 (CCL21) and SPARC-like protein 1 (SPARCL1/MAST9/hevin/SC-1) are associated with various biological behavior in the development of cancers. Although the expression of CCL21 and SPARCL1 is downregulated in many solid tumors, their roles in ovarian cancer and their associations with drug r...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.1819

    authors: Yin F,Liu X,Li D,Wang Q,Zhang W,Li L

    更新日期:2013-04-01 00:00:00

  • DKK3 knockdown confers negative effects on the malignant potency of head and neck squamous cell carcinoma cells via the PI3K/Akt and MAPK signaling pathways.

    abstract::Dickkopf‑related protein 3 (DKK3), which is a member of the Dickkopf WNT signaling pathway inhibitor family, is considered to be a tumor suppressor, due to its reduced expression in cancer cells and its ability to induce apoptosis when overexpressed by adenovirus. However, our previous study demonstrated alternative f...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4667

    authors: Katase N,Nishimatsu SI,Yamauchi A,Yamamura M,Fujita S

    更新日期:2019-03-01 00:00:00

  • Substrate stiffness affects epithelial-mesenchymal transition of cervical cancer cells through miR-106b and its target protein DAB2.

    abstract::The effects of different substrate stiffness were investigated on epithelial-mesenchymal transition (EMT) of cervical cancer cell lines and the role of miR-106b and its target protein DAB2 therein. Cervical cancer cell lines HeLa and SiHa were cultured on artificial substrates with different stiffness prepared using d...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2017.3978

    authors: Piao J,You K,Guo Y,Zhang Y,Li Z,Geng L

    更新日期:2017-06-01 00:00:00

  • Crude extract and solvent fractions of Calystegia soldanella induce G1 and S phase arrest of the cell cycle in HepG2 cells.

    abstract::The representative halophyte Calystegia soldanella (L) Roem. et Schult is a perennial vine herb that grows in coastal dunes throughout South Korea as well as in other regions around the world. This plant has long been used as an edible and medicinal herb to cure rheumatic arthritis, sore throat, dropsy, and scurvy. So...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2017.3836

    authors: Lee JI,Kim IH,Nam TJ

    更新日期:2017-02-01 00:00:00

  • Hyperthermia improves cellular immune response to human hepatocellular carcinoma subsequent to co-culture with tumor lysate pulsed dendritic cells.

    abstract::Dendritic cells play a major role in cellular immunity. The crucial steps of antigen presentation and processing by DCs may be limiting factors for adoptive cellular immunotherapy. Here, we investigated whether hyperthermia of human hepatocellular carcinoma (HCC) cells induces enhanced cytotoxic cellular immune respon...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Schueller G,Stift A,Friedl J,Dubsky P,Bachleitner-Hofmann T,Benkoe T,Jakesz R,Gnant M

    更新日期:2003-06-01 00:00:00

  • Ca549 immunoassay in breast-tissue - comparison with ca15.3 and mca.

    abstract::The relationship between mucin markers and several clinical and pathological characteristics was investigated in breast cancer tissue. CA549, CA15.3 and MCA were measured using commercially available assay methods in 82 primary breast carcinomas and 47 normal glandular breast tissue samples. Similarly to CA15.3 and MC...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.3.4.695

    authors: Gion M,Plebani M,Mione R,Capitanio G,Penzo C,Meo S

    更新日期:1993-10-01 00:00:00

  • Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer.

    abstract::Aurora kinase A (AURKA) regulates the cell cycle checkpoint and maintains genomic integrity. AURKA is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. To investigate the role of AURKA in endometrial cancer, we evaluated t...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2015.2842

    authors: Umene K,Yanokura M,Banno K,Irie H,Adachi M,Iida M,Nakamura K,Nogami Y,Masuda K,Kobayashi Y,Tominaga E,Aoki D

    更新日期:2015-04-01 00:00:00