Anthocyanins induce cell cycle perturbations and apoptosis in different human cell lines.

Abstract:

:To investigate the mechanistic basis for the biological properties of anthocyanins, two aglycone anthocyanins [delphinidin (DY) and cyanidin (CY)] were used to examine their effects on cell cycle progression and on induction of apoptosis in human cancer cells (uterine carcinoma and colon adenocarcinoma cells) and in normal human fibroblasts. These compounds differ in the number and position of hydroxyl groups on the beta ring in the molecular structure. Cellular uptake of anthocyanins was confirmed by HPLC analysis and no metabolites were detected. The clonogenic assay showed that CY induces a dose-dependent growth inhibitory effect only in fibroblasts. This effect was confirmed by flow cytometric analysis, showing a significant reduction of cells in S phase. In contrast, DP inhibited cell growth in normal and tumour cell lines. This event is accompanied in fibroblasts by an accumulation of cells in the S phase suggesting a block in the transition from S to G2 phase. On the other hand, in tumour cell lines we observed a reduction of cells in G1 phase, paralleled by the appearance of a fraction of cells with a hypodiploid DNA content, thus demonstrating an apoptotic effect by DP. The occurrence of apoptosis induced by DP was confirmed by morphological and biochemical features, including nuclear condensation and fragmentation, annexin V staining, DNA laddering and poly(ADP-ribose) polymerase-1-proteolysis. Furthermore, the mitochondrial membrane potential of apoptotic cells after treatment with DP was significantly lost. The different effects exerted by DP as compared with CY suggest that the presence of the three hydroxyl groups on the beta ring in the molecular structure of DP may be important for its greater biological activity.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Lazzè MC,Savio M,Pizzala R,Cazzalini O,Perucca P,Scovassi AI,Stivala LA,Bianchi L

doi

10.1093/carcin/bgh138

keywords:

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

1427-33

issue

8

eissn

0143-3334

issn

1460-2180

pii

bgh138

journal_volume

25

pub_type

杂志文章
  • Absence of DNA breaks during repair of DNA-protein cross-links induced by the mycotoxin botryodiplodin in mammalian cells.

    abstract::Botryodiplodin induces DNA-protein cross-links (DPC) in mammalian cells in culture. Removal of the mycotoxin followed by incubation of cells in fresh medium leads to the gradual disappearance of DPC. The present experiments attempted to determine to what extent the repair mechanism acts through a system involving tran...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/5.10.1375

    authors: Moulé Y,Darracq N

    更新日期:1984-10-01 00:00:00

  • Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment.

    abstract::Basic in vitro systems can be used to model and assess complex diseases, such as cancer. Recent advances in this field include the incorporation of multiple cell types and extracellular matrix proteins into three-dimensional (3D) models to recapitulate the structure, organization and functionality of live tissue in si...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgu108

    authors: Herrmann D,Conway JR,Vennin C,Magenau A,Hughes WE,Morton JP,Timpson P

    更新日期:2014-08-01 00:00:00

  • Diethylnitrosamine administration in vivo increases hepatic poly(ADP-ribose) levels in rats: results of a modified technique for poly(ADP-ribose) measurement.

    abstract::Poly(ADP-ribose) (polymer) is enzymatically synthesized on nuclear proteins in response to DNA strand breaks. NAD+ is the substrate for this reaction, which is catalyzed by poly(ADP-ribose)polymerase. This post-translational modification occurs in response to DNA strand breaks and is thought to play an important role ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.12.2513

    authors: Rawling JM,Driscoll ER,Poirier GG,Kirkland JB

    更新日期:1993-12-01 00:00:00

  • Excretion of DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, PhIP-dG, PhIP-DNA and DiMeIQx-DNA from the rat.

    abstract::The heterocyclic aromatic amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) are formed during frying of meat. PhIP and 4,8-DiMeIQx have, after metabolic activation, been shown to form adducts with DNA at the C8 of guanine both in vitro and...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.8.1555

    authors: Frandsen H

    更新日期:1997-08-01 00:00:00

  • Immunochemical comparison of human and rhesus monkey liver microsomal and the hepatocellular carcinoma-induced human serum epoxide hydrolases (preneoplastic antigens): basis for an enzyme-linked immunoabsorbent assay.

    abstract::An antibody (anti-EH) specific for microsomal epoxide hydrolase (mEH) from rhesus monkey liver has been used to test the immunochemical relationship between human liver mEH and the serum EH levels in human patients with hepatocellular carcinoma (HCC). Immunoblots of separated rhesus monkey and human liver microsomal p...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/10.2.343

    authors: Moody DE,Hammock BD,Ruebner BH,Hillman DW,Hillman JH

    更新日期:1989-02-01 00:00:00

  • An integrative genomic approach in oesophageal cells identifies TRB3 as a bile acid responsive gene, downregulated in Barrett's oesophagus, which regulates NF-kappaB activation and cytokine levels.

    abstract::Reflux of gastroduodenal contents and consequent inflammatory responses are associated with the development of Barrett's oesophagus (BO) and the promotion of oesophageal adenocarcinoma (OAC). Deregulation of inflammatory processes is a hallmark of oesophageal cancer. In this study, we aimed to investigate (i) the tran...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq036

    authors: Duggan SP,Behan FM,Kirca M,Smith S,Reynolds JV,Long A,Kelleher D

    更新日期:2010-05-01 00:00:00

  • Effect of tumour promoters and non-genotoxic carcinogens on terminal differentiation and proliferation in mouse teratoma XB2 cells cultured in low calcium medium.

    abstract::XB2 cells, a teratocarcinoma derived cell line of keratinocyte lineage, have been shown to proliferate and differentiate in low calcium medium (0.03 mM Ca2+) at a density of 500 cells/9.6 cm2 without the need for fibroblast feeder layers or conditioned medium. The degree of differentiation can be assessed by measureme...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.3.371

    authors: Hewitt SD,Duffy PA,Orton TC,Garner RC

    更新日期:1990-03-01 00:00:00

  • Increased risk of prostate cancer and benign prostatic hyperplasia associated with transforming growth factor-beta 1 gene polymorphism at codon10.

    abstract::Transforming growth factor-beta 1 (TGF-beta1) plays a significant role in regulating the proliferation and apoptosis of prostate epithelial and stromal cells. We explored the association between the T (Leu) to C (Pro) polymorphism at codon10 of the TGF-beta1 gene (TGFB1) and the risk of prostate cancer (PCa) or benign...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg197

    authors: Li Z,Habuchi T,Tsuchiya N,Mitsumori K,Wang L,Ohyama C,Sato K,Kamoto T,Ogawa O,Kato T

    更新日期:2004-02-01 00:00:00

  • Strain-dependent lung tumor formation in mice transplacentally exposed to 3-methylcholanthrene and post-natally exposed to butylated hydroxytoluene.

    abstract::The carcinogenic effects of in utero exposure to 3-methylcholanthrene (MC) have been demonstrated in the tumor-resistant C57BL/6 (B6) and DBA (D2) strains of mice. In this study, we determined the effects of in utero exposure to MC in BALB/c mice, a strain which demonstrates greater susceptibility to lung tumor induct...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.11.2159

    authors: Gressani KM,Leone-Kabler S,O'Sullivan MG,Case LD,Malkinson AM,Miller MS

    更新日期:1999-11-01 00:00:00

  • Diffusion of dialkylnitrosamines into the rat esophagus as a factor in esophageal carcinogenesis.

    abstract::To indicate how readily nitrosamines (NAms) diffuse into the esophagus, we measured diffusion rate (flux) through rat esophagus of dialkyl-NAms using side-by-side diffusion apparatuses. Mucosal and serosal flux at 37 degrees C of two NAms, each at 50 microM, was followed for 90 min by gas chromatography-thermal energy...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.5.825

    authors: Haorah J,Miller DW,Brand R,Smyrk TC,Wang X,Chen SC,Mirvish SS

    更新日期:1999-05-01 00:00:00

  • Candidate gene association analysis of acute lymphoblastic leukemia identifies new susceptibility locus at 11p15 (LMO1).

    abstract::To determine the contribution of susceptibility loci in explaining the genetic basis of acute lymphoblastic leukemia (ALL), we genotyped 29 high-potential candidate genes with 672 tagged single-nucleotide polymorphisms (SNPs) in a sample (163 cases and 251 healthy controls) of Caucasian children. Fifty SNPs in 15 gene...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr091

    authors: Beuten J,Gelfond JA,Piwkham D,Pollock BH,Winick NJ,Collier AB 3rd,Tomlinson GE

    更新日期:2011-09-01 00:00:00

  • Selective changes of retroelement expression in human prostate cancer.

    abstract::Retroelements constitute a large part of the human genome. These sequences are mostly silenced in normal cells, but genome-wide DNA hypomethylation in cancers might lead to their re-expression. Whether this re-expression really occurs in human cancers is largely unkown. We therefore investigated expression and DNA met...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr181

    authors: Goering W,Ribarska T,Schulz WA

    更新日期:2011-10-01 00:00:00

  • Acute changes in liver gene expression in the N-nitrosodiethylamine-treated rat.

    abstract::We constructed a complementary DNA (cDNA) library from mRNAs of rat liver induced by an initiating dose of a chemical carcinogen, N-nitrosodiethylamine (DEN). Using a differential hybridization with cDNA probes prepared from mRNAs of control and DEN-treated rat liver, eight cDNAs of which expression was altered by an ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.8.1759

    authors: Suzuki T,Imagawa M,Yamada R,Yokoyama K,Kondo S,Itakura K,Muramatsu M

    更新日期:1994-08-01 00:00:00

  • Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas.

    abstract::The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well do...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi130

    authors: Ma X,Chen K,Huang S,Zhang X,Adegboyega PA,Evers BM,Zhang H,Xie J

    更新日期:2005-10-01 00:00:00

  • Induction and time course of DNA single-strand breaks in lymphocytes from patients treated with dacarbazine.

    abstract::Dacarbazine (DTIC) is an antitumor agent, used for the treatment of metastatic melanoma. It is metabolized to an alkylating agent which reacts with DNA. A fast and simple method was developed in order to measure drug-induced DNA damage in lymphocytes isolated from frozen blood samples of treated patients. The level of...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.6.1153

    authors: Walles SA,Ringborg U

    更新日期:1991-06-01 00:00:00

  • Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells.

    abstract::The androgen receptor (AR) is involved in the development and progression of prostate cancer. In order to find new compounds that may present novel mechanisms to attenuate the function of AR, we investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prost...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/22.3.409

    authors: Xing N,Chen Y,Mitchell SH,Young CY

    更新日期:2001-03-01 00:00:00

  • Induction of apoptosis in the lung but not in the liver of rats receiving intra-tracheal instillations of chromium(VI).

    abstract::Several studies have shown that hexavalent chromium [Cr(VI)] induces apoptosis in a variety of in vitro test systems. We instilled intra-tracheally either saline or sodium dichromate (0.25 mg/kg body weight), for three consecutive days, to Sprague-Dawley rats. TUNEL analyses showed a marked increase of the apoptotic i...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.4.587

    authors: D'Agostini F,Izzotti A,Bennicelli C,Camoirano A,Tampa E,De Flora S

    更新日期:2002-04-01 00:00:00

  • MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL.

    abstract::MicroRNAs (miRNAs) are small non-coding RNAs that are involved in different biological processes by suppressing target gene expression. Altered expression of miR-30a-5p has been reported in colon carcinoma. To elucidate its potential biological role in colon cancer, miR-30a-5p was overexpressed via a lentiviral vector...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs020

    authors: Baraniskin A,Birkenkamp-Demtroder K,Maghnouj A,Zöllner H,Munding J,Klein-Scory S,Reinacher-Schick A,Schwarte-Waldhoff I,Schmiegel W,Hahn SA

    更新日期:2012-04-01 00:00:00

  • Substituted hydroxyphenanthrenes in opium pyrolysates implicated in oesophageal cancer in Iran: structures and in vitro metabolic activation of a novel class of mutagens.

    abstract::Previous epidemiological and laboratory studies have indicated an association between the ingestion of opium pyrolysates, dietary deficiencies and the high incidence of oesophageal cancer in subjects in north-east Iran. Pyrolysates of opium, and particularly of morphine, a major opium alkaloid, were both shown to cont...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.10.1423

    authors: Friesen M,O'Neill IK,Malaveille C,Garren L,Hautefeuille A,Bartsch H

    更新日期:1987-10-01 00:00:00

  • LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway.

    abstract::Hepatocellular carcinoma (HCC) is one of the leading causes for cancer related mortality worldwide. Poor prognosis of HCC patients is mainly due to frequent metastasis and recurrence. Deregulation of metastasis suppressors in malignant cells plays critical roles during cancer metastasis. Thus, novel metastasis suppres...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgv108

    authors: Luo Q,Wang C,Jin G,Gu D,Wang N,Song J,Jin H,Hu F,Zhang Y,Ge T,Huo X,Chu W,Shu H,Fang J,Yao M,Gu J,Cong W,Qin W

    更新日期:2015-10-01 00:00:00

  • Inhibitory effects of 17beta-estradiol and 4-n-octylphenol on 7,12-dimethylbenz[a]anthracene-induced mammary tumor development in human c-Ha-ras proto-oncogene transgenic rats.

    abstract::Experiments were conducted to determine whether the natural estrogen and an environmental compound with estrogenic action, 4-n-octylphenol (4nOP), could modify tumor development in human c-Ha-ras proto-oncogene transgenic (Tg) rats which are highly susceptible to mammary and skin carcinogens. Female and male Tg and no...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.7.1209

    authors: Han BS,Fukamachi K,Takasuka N,Ohnishi T,Maeda M,Yamasaki T,Tsuda H

    更新日期:2002-07-01 00:00:00

  • Dysregulation of WNT/CTNNB1 and PI3K/AKT signaling in testicular stromal cells causes granulosa cell tumor of the testis.

    abstract::Synergistic effects of dysregulation of the WNT/CTNNB1 and phosphatidylinositol 3-kinase (PI3K)/AKT pathways are thought to be important for the development and progression of many forms of cancer, including the granulosa cell tumor of the ovary. Sustained WNT/CTNNB1 signaling in Sertoli cells causes testicular degene...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgp051

    authors: Boyer A,Paquet M,Laguë MN,Hermo L,Boerboom D

    更新日期:2009-05-01 00:00:00

  • Limited capacity for the removal of O6-methylguanine and its regeneration in a human lymphoma line.

    abstract::The Raji human lymphoma line is able to remove O6-methylguanine (O6MeG) lesions introduced by treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The reaction has a rapid phase in which approximately 40% of the O6MeG is removed in the first 10 min. The capacity of cells for rapid O6MeG removal is limi...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.12.1293

    authors: Sklar R,Brady K,Strauss B

    更新日期:1981-01-01 00:00:00

  • Stimulation of DNA synthesis and c-fos mRNA expression in primary rat hepatocytes by estrogens.

    abstract::The mechanism(s) of tumour promotion in liver by estrogens is not well understood although growth stimulation is known to be one important element of their action. As a basis for studying mechanisms of growth control by estrogens, effects of both natural and synthetic estrogens on DNA synthesis and protooncogene c-fos...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/22.9.1473

    authors: Lee CH,Edwards AM

    更新日期:2001-09-01 00:00:00

  • Mutagenicity and synthesis of alpha-substituted N-nitrosamines: derivatives with dithiocarbamic acid.

    abstract::Disulfiram (DSF) can considerably alter the organotropy of chemical carcinogens. For N-nitrosodimethylamine and for N-nitrosodiethylamine the organotropy is shifted from the liver to the nasal cavity or the oesophagus, respectively. Whereas the influence of DSF or its metabolites on enzyme systems has been studied, li...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.5.563

    authors: Pool BL,Bertram B,Wiessler M

    更新日期:1982-01-01 00:00:00

  • Unmasking the impact of Rictor in cancer: novel insights of mTORC2 complex.

    abstract::Genomic alterations affecting components of the mechanistic target of rapamycin (mTOR) pathway are found rather frequently in cancers, suggesting that aberrant pathway activity is implicated in oncogenesis of different tumor types. mTOR functions as the core catalytic kinase of two distinct complexes, mTOR complex 1 (...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgy086

    authors: Gkountakos A,Pilotto S,Mafficini A,Vicentini C,Simbolo M,Milella M,Tortora G,Scarpa A,Bria E,Corbo V

    更新日期:2018-07-30 00:00:00

  • The induction of Ouar-mutations in nontransformable CVP3SC6 mouse fibroblasts.

    abstract::A line of C3H mouse fibroblasts designated CVP3SC6 (CVP) was found to be nonresponsive to the induction of morphological transformation by the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) and its BaP-7,8-diol and BaP-diol-epoxide derivates. This cell line was, however, susceptible to BaP-induced mutation to ou...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.9.963

    authors: Gehly EB,Heidelberger C

    更新日期:1982-01-01 00:00:00

  • The effect of fibre source and fermentation on the apparent hydrophobic binding properties of wheat bran preparations for the mutagen 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline (MeIQx).

    abstract::Preparations of dietary fibre have an ability to bind potentially toxic compounds in vitro, but it is unclear how the measured binding properties are a reflection of either the relative affinity of such compounds for fibre or the saturation binding capacity of the fibre. Cooking and processing of foods and fermentatio...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.2.209

    authors: Ryden P,Robertson JA

    更新日期:1995-02-01 00:00:00

  • Modulation of growth and cell turnover of preneoplastic lesions and of prostaglandin levels in rat pancreas by dietary fish oil.

    abstract::In the present study the modulating effects of dietary fish oil (MaxEPA) on unsaturated fat-promoted pancreatic carcinogenesis in azaserine-treated rats were investigated. Three groups of 20 rats (each group comprised five saline-treated and 15 azaserine-treated animals) were fed an AIN76-based purified diet containin...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.10.2107

    authors: Appel MJ,Woutersen RA

    更新日期:1994-10-01 00:00:00

  • Altered regulation of growth and expression of differentiation-associated keratins in benign mouse skin tumors.

    abstract::Alterations in the pattern of epidermal cell differentiation and proliferation in mouse skin and benign skin tumors were studied by two-color immunofluorescence using monospecific antibodies. Replicating cells were identified by 5-bromo-deoxyuridine (BrdU) pulse-labeling and differentiating cells by keratins K1 and K1...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.11.2063

    authors: Huitfeldt HS,Heyden A,Clausen OP,Thrane EV,Roop D,Yuspa SH

    更新日期:1991-11-01 00:00:00