Abstract:
INTRODUCTION:Natural herbal compounds with novel actions different from existing breast cancer (BCa) treatment modalities are attractive for improving therapeutic efficacy and safety. We have recently shown that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) induced S-phase arrest in prostate cancer (PCa) cells through inhibiting DNA replicative synthesis and G(1) arrest, in addition to inducing cell death at higher levels of exposure. We and others have shown that PGG through intraperitoneal (i.p.) injection exerts a strong in vivo growth suppression of human PCa xenograft models in athymic nude mice. This study aims to test the hypothesis that the novel targeting actions of PGG are applicable to BCa cells, especially those lacking proven druggable targets. METHODS:Mono-layer cell culture models of p53-wild type estrogen receptor (ER)-dependent MCF-7 BCa cells and p53-mutant ER-/progesterone receptor (PR)- and Her2-regular (triple-negative) MDA-MB-231 BCa were exposed to PGG for a comprehensive investigation of cellular consequences and molecular targets/mediators. To test the in vivo efficacy, female athymic mice inoculated with MDA-MB-231 xenograft were treated with 20mg PGG/kg body weight by daily gavage starting 4 days after cancer cell inoculation. RESULTS:Exposure to PGG induced S-phase arrest in both cell lines as indicated by the lack of 5-bromo2'-deoxy-uridine (BrdU) incorporation into S-phase cells as well as G(1) arrest. Higher levels of PGG induced more caspase-mediated apoptosis in MCF-7, in strong association with induction of P53 Ser(15) phosphorylation, than in MDA-MB-231 cells. The cell cycle arrests were achieved without an induction of cyclin dependent kinase (CDK) inhibitory proteins P21(Cip1) and P27(Kip1). PGG treatment led to decreased cyclin D1 in both cell lines and over-expressing cyclin D1 attenuated G(1) arrest and hastened S arrest. In serum-starvation synchronized MCF-7 cells, down-regulation of cyclin D1 was associated with de-phosphorylation of retinoblastoma (Rb) protein by PGG shortly before G(1)-S transition. In vivo, oral administration of PGG led to a greater than 60% inhibition of MDA-MB231 xenograft growth without adverse effect on host body weight. CONCLUSIONS:Our in vitro and in vivo data support PGG as a potential drug candidate for breast cancer with novel targeting actions, especially for a triple negative BCa xenograft model.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Chai Y,Lee HJ,Shaik AA,Nkhata K,Xing C,Zhang J,Jeong SJ,Kim SH,Lu Jdoi
10.1186/bcr2634subject
Has Abstractpub_date
2010-01-01 00:00:00pages
R67issue
5eissn
1465-5411issn
1465-542Xpii
bcr2634journal_volume
12pub_type
杂志文章abstract:INTRODUCTION:Breast cancer is a worldwide health problem and the leading cause of cancer death among females. We previously identified Jumonji domain containing 2A (JMJD2A) as a critical mediator of breast cancer proliferation, migration and invasion. We now report that JMJD2A could promote breast cancer progression th...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3667
更新日期:2014-05-30 00:00:00
abstract:INTRODUCTION:The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality. METHODS:We evaluated the association between semi-q...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3486
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:Incidence of breast cancer is increasing around the world and it is still the leading cause of cancer mortality in low- and middle-income countries. We utilized Swedish nationwide registers to study breast cancer incidence and case fatality to disentangle the effect of socioeconomic position (SEP) and immi...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3086
更新日期:2012-01-06 00:00:00
abstract:INTRODUCTION:The chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as a tumor suppressor in a mouse model. The CHD5 locus at 1p36 is deleted, and its mutation has been detected in breast cancer. We, therefore, evaluated whether CHD5 plays a role in human breast cancer. METHODS:We screened...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr3182
更新日期:2012-05-08 00:00:00
abstract:BACKGROUND:Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. T...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-018-0939-5
更新日期:2018-02-06 00:00:00
abstract::RAD51C is an integral part of the DNA double-strand repair through homologous recombination, and monoallelic mutations were found in ~1.3% of BRCA1/2-negative breast cancer (BC) and/or ovarian cancer (OC) families. Several studies confirmed the occurrence of RAD51C mutations predominantly in BC and/or OC families, alt...
journal_title:Breast cancer research : BCR
pub_type: 信件
doi:10.1186/bcr3589
更新日期:2013-12-20 00:00:00
abstract:INTRODUCTION:The invasive, mesenchymal phenotype of CD44posCD24neg breast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44neg/lowCD24pos breast cancer cells lack the ability to give rise to their invasive CD44posCD24ne...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2449
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Aberrant expression of the embryonic stem cell marker Sox2 has been reported in breast cancer (BC). We previously identified two phenotypically distinct BC cell subsets separated based on their differential response to a Sox2 transcription activity reporter, namely the reporter-unresponsive (RU) and the mo...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0470-2
更新日期:2014-11-08 00:00:00
abstract:INTRODUCTION:Laboratory and epidemiologic studies have suggested a modifying effect of cardiac glycosides (for example, digoxin and digitoxin) on cancer risk. We explored the association between digoxin treatment and invasive breast cancer incidence among postmenopausal Danish women. METHODS:We used Danish registries ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2205
更新日期:2008-01-01 00:00:00
abstract::The role of specific dietary factors in breast cancer causation is not completely resolved. Results from prospective studies do not support the concept that fat intake in middle life has a major relation to breast cancer risk. However, weight gain in middle life contributes substantially to breast cancer risk. Alcohol...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
doi:10.1186/bcr909
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondria...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0567-2
更新日期:2015-04-25 00:00:00
abstract:BACKGROUND:Women with breast cancer who have multiple affected relatives are more likely to have inherited genetic risk factors for the disease. All the currently known genetic risk factors for breast cancer account for less than half of the average familial risk. Furthermore, the genetic factor(s) underlying an increa...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0825-6
更新日期:2017-03-16 00:00:00
abstract:INTRODUCTION:Metastasis is a common event and the main cause of death in cancer patients. Lymphangiogenesis refers to the formation of new lymphatic vessels and is thought to be involved in the development of metastasis. Sunitinib is a multi-kinase inhibitor that blocks receptor tyrosine kinase activity, including that...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2903
更新日期:2011-06-21 00:00:00
abstract:INTRODUCTION:PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α) somatic mutations are the most common genetic alteration in breast cancer (BC). Their prognostic value and that of the phosphatidylinositol 3-kinase (PI3K) pathway in BC remains only partly defined. The effect of PIK3CA mutations ...
journal_title:Breast cancer research : BCR
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/bcr3683
更新日期:2014-06-30 00:00:00
abstract:INTRODUCTION:The potential of applying data analysis tools to microarray data for diagnosis and prognosis is illustrated on the recent breast cancer dataset of van 't Veer and coworkers. We re-examine that dataset using the novel technique of logical analysis of data (LAD), with the double objective of discovering patt...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1512
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Estrogen receptor-alpha (ER-alpha) and progesterone receptor (PgR) are consolidated predictors of response to hormonal therapy (HT). In contrast, little information regarding the role of estrogen receptor-beta (ER-beta) in various breast cancer risk groups treated with different therapeutic regimens is ava...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2139
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Triple-negative breast cancer (TNBC) is a subtype of highly malignant breast cancer with poor prognosis. TNBC is not amenable to endocrine therapy and often exhibit resistance to current chemotherapeutic agents, therefore, further understanding of the biological properties of these cancer cells and develop...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-014-0434-6
更新日期:2014-09-11 00:00:00
abstract::The increasing importance of signal transducer and activator of transcription 3 (STAT3) expression in human cancers has led several laboratories to examine in detail the expression of one of its major negative regulators in oncogenesis--the T-cell protein tyrosine phosphatase, nonreceptor type 2 (PTPN2). A recent pape...
journal_title:Breast cancer research : BCR
pub_type: 评论,杂志文章,评审
doi:10.1186/bcr3437
更新日期:2013-07-31 00:00:00
abstract:BACKGROUND:The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. METHODS:We have c...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr419
更新日期:2002-01-01 00:00:00
abstract:INTRODUCTION:We showed in a previous study that prenylated proteins play a role in estradiol stimulation of proliferation. However, these proteins antagonize the ability of estrogen receptor (ER) alpha to stimulate estrogen response element (ERE)-dependent transcriptional activity, potentially through the formation of ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr956
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The ataxia-telangiectasia mutated (ATM) gene (MIM ID 208900) encodes a protein kinase that plays a significant role in the activation of cellular responses to DNA double-strand breaks through subsequent phosphorylation of central players in the DNA damage-response pathway. Recent studies have confirmed tha...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
doi:10.1186/bcr2919
更新日期:2011-07-25 00:00:00
abstract:BACKGROUND:Although parity and age at first pregnancy are among the most known extrinsic factors that modulate breast cancer risk, their impact on the biology of subsequent breast cancer has never been explored in depth. Recent data suggest that pregnancy-induced tumor protection is different according to breast cancer...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1111-6
更新日期:2019-02-15 00:00:00
abstract:BACKGROUND:Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal wom...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-019-1128-x
更新日期:2019-03-28 00:00:00
abstract:BACKGROUND:The relationship between breast cancer and thyroid diseases is controversial. Discrepant results have been reported in the literature. The incidences of autoimmune and nonautoimmune thyroid diseases were investigated in patients with breast cancer and age-matched control individuals without breast or thyroid...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr609
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Chromogenic in situ hybridization (CISH) is emerging as a practical, cost-effective, and valid alternative to fluorescent in situ hybridization in testing for gene alteration, especially in centers primarily working with immunohistochemistry (IHC). METHODS:We assessed Her-2/neu alteration using CISH on form...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr915
更新日期:2004-01-01 00:00:00
abstract::The protective effect of an early full-term pregnancy is a well established phenomenon; in contrast, the molecular and cell-specific mechanisms that govern parity-specific changes in the mammary gland have not been well described. Recent studies signify a dramatic advance in our understanding of this phenomenon, and i...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr603
更新日期:2003-01-01 00:00:00
abstract::This cross-sectional investigation in Hawaii explored the relation between soy foods and mammographic characteristics using two food frequency questionnaires and a computer-assisted density assessment method. Japanese and Chinese women reported significantly greater soy food intake than Caucasian women. Whereas soy in...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr285
更新日期:2001-01-01 00:00:00
abstract:INTRODUCTION:Breast cancer is genetically and clinically a heterogeneous disease. However, the exact contribution of different cell types and oncogenic mutations to this heterogeneity are not well understood. Recently, we discovered an interaction between Wnt and integrin-linked kinase (ILK) within the signaling cascad...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr2592
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:In breast cancer, BRCA promoter hypermethylation and BRCA germline mutations are said to occur together rarely, but this property has not yet been translated into a clinical test. Our aim in this study was to investigate the diagnostic value of BRCA1/2 methylation in distinguishing breast carcinomas of BRCA1...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-017-0856-z
更新日期:2017-05-31 00:00:00
abstract:INTRODUCTION:Breast cancer is the most common female malignancy worldwide and, despite improvements in treatment modalities, there are increased chances of recurrence and metastasis in a substantial number of cases and it remains one of the major causes of mortality among female cancer patients. Anaplastic lymphoma kin...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/s13058-015-0610-3
更新日期:2015-09-17 00:00:00