• BMB Reports
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• v.39 no.4
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• pp.448-451
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• 2006

Chemopreventive and cytotoxic effect of genistein against human breast cancer cell lines was investigated. Genistein inhibited cell proliferation in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity was inhibited by genistein in a concentrationdependent manner. Genistein significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxy-genase-2 activity and protein expression at the concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition, ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after 6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results suggest that genistein could be of therapeutic value in preventing human breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.257-263
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• 2014

Background: Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, has been implicated as a critical factor influencing tumor related angiogenesis. The aim of present study was to evaluate the relationship between VEGF +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancer in Punjab, India. Materials and Methods: We screened DNA samples of 192 sporadic breast cancer patients and 192 unrelated healthy, gender and age matched control individuals for VEGF +936C>T and +405C>G polymorphisms using the PCR-RFLP method. Results: For the VEGF +405C>G polymorphism, we observed significantly increased frequency of GG genotype in cases as compared to controls and strong association of +405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%CI 1.41-6.65; p=0.003). For the +936C>T polymorphism, significant associations of CT and combined CT+TT genotypes were observed with elevated risk of breast cancer (p=0.021; 0.023). The combined genotype combinations of GG-CC and GG-CT of +405C>G and +936C>T polymorphisms were found to be significantly associated with increased risk of breast cancer (p=0.04; 0.0064). Conclusions: The findings of the present study indicated significant associations of VEGF +936C>T and +405C>G polymorphisms with increased breast cancer risk in patients from Punjab, North India.

• Genomics & Informatics
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• v.21 no.1
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• pp.11.1-11.5
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• 2023

Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564 (with an average of 30,591) compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7553-7558
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• 2014

The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZ and Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has been shown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports have indicated that abnormal hiwi expression is associated with poorer prognosis of multiple types of human cancers, including examples in the breast. However, little is known about details of the oncogenic role of hiwi in breast cancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantly higher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymph node metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDA-MB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role of hiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up- or down-regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting roles of hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the present study confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and provided e vidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.313-319
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• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1075-1079
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• 2014

MicroRNA expression is a research focus in studies of tumors. This article concentrates attention on potential links between tumors caused by mouse mammary tumor virus (MMTV) and human breast cancer, in order to provide theoretical basis for using mouse model to search for miRNA effects mediated by Wnt/beta-catenin signaling in human breast cancer. By analyzing interactions between miRNAs and the Wnt/beta-catenin signaling pathway in breast cancer, we hope to casts light on more biological functions of miRNAs in the process of tumor formation and growth and to explore their potential value in cancer diagnosis, prognosis and treatment. Our endeavor aimed at providing theoretical basis for finding safer, more effective methods for treatment of human breast cancer at the miRNA molecular level.

• Journal of Breast Disease
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• v.6 no.2
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• pp.39-45
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• 2018

Purpose: Dieckol, a phlorotannin compound isolated from Ecklonia cava, has been reported to have antioxidant, antiviral, anti-inflammatory, and anticancer properties. The purpose of this study was to investigate its anticancer effects on human breast cancer cell lines. Methods: In this study, the viability of two human breast cancer cell lines SK-BR-3 and MCF-7 was investigated after dieckol treatment using a WST-1 assay. Apoptosis and cell cycle distribution were assayed via Annexin V-fluorescein isothiocyanate and propidium iodide staining followed by flow cytometric analysis. Immunoblotting analysis was also performed using Bax/Bcl-2 to determine whether the dieckol-induced apoptosis was mediated by the intrinsic apoptotic pathway. Results: In a dose dependent manner, dieckol reduced the number of viable cells and increased the number of apoptotic cells. The effect of dieckol on the cell cycle distribution was analyzed using flow cytometry. Dieckol treatment significantly increased the percentage of MCF-7 and SK-BR-3 in the G2/M phase. Immunoblot analysis revealed that 24 hours of dieckol exposure increased the Bax/Bcl-2 ratio. Conclusion: Dieckol induced cytotoxicity in MCF-7 and SK-BR-3 human breast cancer cells inducing apoptosis and cell cycle arrest. Therefore, it is suggested that dieckol may be a potential therapeutic agent for breast cancer.

• Molecules and Cells
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• v.39 no.9
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• pp.663-668
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• 2016

The oncogene nuclear receptor coactivator amplified in breast cancer 1 (AIB1) is a transcriptional coactivator, which is overexpressed in various types of human cancers, including breast cancer. However, the molecular mechanisms regulating AIB1 function remain largely unknown. In this study, we present evidence demonstrating that AIB1 is acetylated by MOF in human breast cancer cells. Moreover, we also found that the acetylation of AIB1 enhances its function in promoting breast cancer cell proliferation. We further showed that the acetylation of AIB1 is required for its recruitment to E2F1 target genes by E2F1. More importantly, we found that the acetylation levels of AIB1 are greatly elevated in human breast cancer cells compared with that in non-cancerous cells. Collectively, our results shed light on the molecular mechanisms that regulate AIB1 function in breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5327-5332
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• 2012

In this review, we describe the patterns of known immunological components in breast milk and examine the relationship between breastfeeding and reduced risk of breast cancer. The top risk factors for breast cancer are a woman's age and family history, specifically having a first-degree relative with breast cancer. Women that have a history of breastfeeding have been shown to have reduced rates of breast cancer. Although the specific cause has not been elucidated, previous studies have suggested that breastfeeding reduces the risk of breast cancer primarily through two mechanisms: the differentiation of breast tissue and reduction in the lifetime number of ovulatory cycles. In this context, one of the primary components of human milk that is postulated to affect cancer risk is alpha-lactalbumin. Tumour cell death can be induced by HAMLET (a human milk complex of alpha-lactalbumin and oleic acid). HAMLET induces apoptosis only in tumour cells, while normal differentiated cells are resistant to its effects. Therefore, HAMLET may provide safe and effective protection against the development of breast cancer. Mothers should be encouraged to breastfeed their babies because the complex components of human milk secretion make it an ideal food source for babies and clinical evidence has shown that there is a lower risk of breast cancer in women who breastfed their babies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5577-5582
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• 2014

Objective: To observe the effects of metastasis-associated tumor gene family 2 (MTA2) depletion on human breast cancer cell proliferation and metastasis. Methods: A short-hairpin RNA targeting MTA2 was chemically synthesized and transfected into a lentivirus to construct Lv-shMTA2 for infection into the MDA-MB231 human breast cancer cell line. At 48 hours after infection cells were harvested and mRNA and protein levels of MTA2 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell viability and metastasis were assessed by CCK-8, wound-healing assay and Transwell assay, respectively. In addition, a xenograft model of human breast cancer was constructed to investigate cancerous cell growth and capacity for metastasis. Results: After infection with Lv-shMTA2, mRNA and protein levels of MTA2 was significantly reduced (p<0.05) and MDA-MB231 cell proliferation and metastasis were inhibited (p<0.05). In addition, mean tumor size was smaller than that in control group nude mice (p<0.05) and numbers of metastatic deposits in lung were lower than in control group mice (p<0.05). Depletion of MTA2 affected MMP-2 and apoptosis-related protein expression. Conclusions: For the first time to our knowledge we showed that MTA2 depletion could significantly inhibit human breast cancer cell growth and metastasis, implying that MTA2 might be involved in the progression of breast cancer. The role of MTA2 in breast cancer growth and metastasis might be linked with regulation of matrix metalloproteinase and apoptosis.