• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3757-3760
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• 2013

MicroRNAs (miRNAs) are small, non-coding RNAs (18-25 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In this context, the present study aimed to evaluate the in vitro effects of miR-485 mimics in breast carcinoma T47D cells. Forty-eight hours after T47D cells were transfected with miR-485 mimics, an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects on cell viability. Colony formation and cell migration assays were adopted to determine whether miR-485 affects the proliferation rates and cell migration of breast carcinoma T47D cells. Our results showed that ectopic expression of miR-485 resulted in a significant decrease in cell growth, cell colony formation, and cell migration. These findings suggest that miR-485 might play an important role in breast cancer by suppressing cell proliferation and migration.

• Molecules and Cells
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• v.43 no.4
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• pp.384-396
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• 2020

Breast cancer is one of the most common life-threatening malignancies and the top cause of cancer deaths in women. Although many conventional therapies exist for its treatment, breast cancer still has many handicaps to overcome. Cancer stem cells (CSCs) are a well-known cause of tumor recurrences due to the ability of CSCs for self-renewal and differentiation into cell subpopulations, similar to stem cells. To fully treat breast cancer, a strategy for the treatment of both cancer cells and CSCs is required. However, current strategies for the eradication of CSCs are non-specific and have low efficacy. Therefore, surface biomarkers to selectively treat CSCs need to be developed. Here, 34 out of 641 surface biomarkers on CSCs were identified by proteomic analysis between the human breast adenocarcinoma cell line MCF-7 and MCF-7-derived CSCs. Among them, carcinoembryonic antigen-related cell adhesion molecules 6 (CEACAM6 or CD66c), a member of the CEA family, was selected as a novel biomarker on the CSC surface. This biomarker was then experimentally validated and evaluated for use as a CSC-specific marker. Its biological effects were assessed by treating breast cancer stem cells (BCSCs) with short hairpin (sh)-RNA under oxidative cellular conditions. This study is the first to evaluate the biological function of CD66c as a novel biomarker on the surface of CSCs. This marker is available as a moiety for use in the development of targeted therapeutic agents against CSCs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7853-7857
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• 2015

Background: Mortality from breast cancer is high in low- and middle-income countries, in part because most patients have advanced stage disease when first diagnosed. Case-finding may be one approach to changing this situation. Materials and Methods: We conducted a pilot study to explore the feasibility of population-based case finding for breast cancer by community health workers (CHWs) using different data collection methods and approaches to management of women found to have breast abnormalities. After training 8 CHWs in breast problem recognition, manual paper data collection and operation of a cell-phone software platform for reporting demographic, history and physical finding information, these CHWs visited 3150 women >age 18 and over they could find-- from 2356 households in 8 villages in rural Bangladesh. By 4 random assignments of villages, data were collected manually (Group 1), or with the cell-phone program alone (Group 2) or with management algorithms (Groups 3 and 4), and women adjudged to have a serious breast problem were shown a motivational video (Group 3), or navigated/accompanied to a breast problem center for evaluation (Group 4). Results: Only three visited women refused evaluation. The manual data acquisition group (1) had missing data in 80% of cases, and took an average of 5 minutes longer to acquire, versus no missing data in the cell phone-reporting groups (2,3 and 4). One woman was identified with stage III breast cancer, and was appropriately treated. Conclusions: Among very poor rural Bangladeshi women, there was very limited reluctance to undergo breast evaluation. The estimated rarity of clinical breast cancer is supported by these population-based findings. The feasibility and efficient use of mobile technology in this setting is supported. Successor studies may most appropriately be trials focusing on improving the suggested benefits of motivation and navigation, on increasing the numbers of cases found, and on stage of disease at diagnosis as the primary endpoint.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.494-502
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• 2018

Breast cancer is currently the most prevalent cancer in women, and its incidence increases every year. Azole antifungal drugs were recently found to have antitumor efficacy in several cancer types. They contain an imidazole (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole) ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we evaluated the effects of azole drugs on cell proliferation, apoptosis, cell cycle, migration, and invasion, and investigated the underlying mechanisms. Clotrimazole and ketoconazole inhibited the proliferation of both cell lines while fluconazole and itraconazole did not. In addition, clotrimazole and ketoconazole inhibited the motility of MDA-MB-231 cells and induced $G_1$-phase arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and immunoblot data. Moreover, Transwell invasion and gelatin zymography assays revealed that clotrimazole and ketoconazole suppressed invasiveness through the inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no significant changes in invasiveness were observed in MCF-7 cells. There were no significant changes in any of the observed parameters with fluconazole or itraconazole treatment in either breast cancer cell line. Taken together, imidazole antifungal drugs showed strong antitumor activity in breast cancer cells through induction of apoptosis and $G_1$ arrest in both MCF-7 and MDA-MB-231 cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic profiles and known toxicity, which can make these generic drugs strong candidates for repositioning as antitumor therapies.

• Journal of Korean Biological Nursing Science
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• v.4 no.2
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• pp.59-68
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• 2002

The purpose of this study was to determine the effect of exercise program on natural killer cell cytotoxic activity(NKCA) in breast cancer patients who had been radiation therapy after surgery. The subjects in the experimental group consisted of 11 breast cancer patients, while the subjects in the control group consisted of 15. Subjects in the experimental group participated in exercise program for 8 weeks. Exercise program consisted of shoulder stretching, arm weight training and treadmill walking exercise. They started to exercise on treadmill for 20 minutes per day, 3 times a week at 40% of maximum heart rate, and increased intensity and duration of exercise so that they were running 30 minutes/day at 60% of maximum heart rate from the 3rd week to the 8th week. Natural killer cell cytotoxic activity were determined before and after the exercise program. For measuring the natural killer cell cytotoxic activity, 8ml to 10ml blood was collected from the subjects. Mononuclear cell was isolated by centrifuge of the blood and cultured by putting $Cr^{51}$, and reacted with target cell, K562 cell. Baseline demographic and medical data were compared between groups with the Fisher's exact test and Mann-Whitney U test. For effects of the exercise program, repeated measures ANOVA was used. The result was as follows; Natural killer cell cytotoxic activity(NKCA) in experimental group comparing with control group significantly increased after the exercise program in case of effector cell : target cell ratio is 100 : 1(p<0.05). The above result suggest that the exercise program for breast cancer patients undergoing radiation therapy after breast surgery may increase the natural killer cell cytotoxic activity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6605-6611
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• 2013

Background: WEE1 is a G2/M checkpoint regulator protein. Various studies have indicated that WEE1 could be a good target for cancer therapy. The main aim of this study was to asssess the tumor suppressive potential of WEE1 silencing in two different breast cancer cell lines, MCF7 which carries the wild-type p53 and MDA-MB468 which contains a mutant type. Materials and Methods: After WEE1 knockdown with specific shRNAs downstream effects on cell viability and cell cycle progression were determined using MTT and flow cytometry analyses, respectively. Real-time PCR and Western blotting were conducted to assess the effect of WEE1 inhibition on the expression of apoptotic (p53) and anti-apoptotic (Bcl2) factors and also a growth marker (VEGF). Results: The results showed that WEE1 inhibition could cause a significant decrease in the viability of both MCF7 and MDA-MB-468 breast cancer cell lines by more than 50%. Interestingly, DNA content assays showed a significant increase in apoptotic cells following WEE1 silencing. WEE1 inhibition also induced upregulation of the apoptotic marker, p53, in breast cancer cells. A significant decrease in the expression of VEGF and Bcl-2 was observed following WEE1 inhibition in both cell lines. Conclusions: In concordance with previous studies, our data showed that WEE1 inhibition could induce G2 arrest abrogation and consequent cell death in breast cancer cells. Moreover, in this study, the observed interactions between the pro- and anti-apoptotic proteins and decrease in the angiogenesis marker expression confirm the susceptibility to apoptosis and validate the tumor suppressive effect of WEE1 inhibition in breast cancer cells. Interestingly, the levels of the sensitivity to WEE1 silencing in breast cancer cells, MCF7 and MDA-MB468, seem to be in concordance with the level of p53 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3681-3685
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• 2012

Background: In breast cancer, estrogen receptors have been demonstrated to interact with transcription factors to regulate target gene expression. However, high-throughput identification of the transcription regulation relationship between transcription factors and their target genes in response to estradiol is still in its infancy. Purpose: Thus, the objective of our study was to interpret the transcription regulation network of MCF7 breast cancer cells exposed to estradiol. Methods: In this work, GSE11352 microarray data were used to identify differentially expressed genes (DEGs). Results: Our results showed that the MYB (v-myb myeloblastosis viral oncogene homolog [avian]), PGR (progesterone receptor), and MYC (v-myc myelocytomatosis viral oncogene homolog [avian]) were hub nodes in our transcriptome network, which may interact with ER and, in turn, regulate target gene expression. MYB can up-regulate MCM3 (minichromosome maintenance 3) and MCM7 expression; PGR can suppress BCL2 (B-cell lymphoma 2) expression; MYC can inhibit TGFB2 (transforming growth factor, beta 2) expression. These genes are associated with breast cancer progression via cell cycling and the $TGF{\beta}$ signaling pathway. Conclusion: Analysis of transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of breast cancer.

• The Korean Journal of Cytopathology
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• v.18 no.2
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• pp.157-160
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• 2007

Granular cell tumor (GCT) of the breast is a rare clinical entity, and is believed to be of schwannian origin and to follow a benign clinical course. A 50-year-old woman presented with a slowly growing mass in the right breast. Fine needle aspiration cytology revealed a cellular smear containing isolated or clustered cells showing round to oval nuclei with abundant oncocytic granular cytoplasm. Nuclei showed a fine granular chromatin pattern and occasional small single nucleoli. Cell boundaries were poorly defined, and naked nuclei were frequently found, Histologically, the tumor showed features of typical GCT, and immunohistochemical staining findings strongly supported the diagnosis. The present study demonstrates that GCT of the breast can mimic malignant lesions of breast both clinically and radiologically. The recognition of its cytologic features and suspicion of this lesion would undoubtedly aid the correct diagnosis of mammary GCT.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4357-4361
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• 2015

Thunbergia Laurifolia Linn. (TL) is one of the most familiar plants in Thai traditional medicine that is used to treat various conditions, including cancer. However, the antitumor activity of TL or its constituents has never been reported at the molecular level to support the folklore claim. The present study was designed to investigate the antitumor effect of an aqueous extract of TL in human breast cancer cells and the possible mechanism(s) of action. An aqueous crude extract was prepared from dried leaves of TL. Folin-Ciocalteu colorimetric assays were used to determine the total phenolic content. Antiproliferative and cell cycle effects were evaluated in human breast adenocarcinoma MCF-7 cells by MTT reduction assay, cell growth inhibition, clonogenic cell survival, and flow cytometric analysis. Free radical generation by the extracts was detected using electron paramagnetic resonance spectroscopy. The exposure of human breast adenocarcinoma MCF-7 cells to a TL aqueous extract resulted in decreases in cell growth, clonogenic cell survival, and cell viability in a concentration-dependent manner with an $IC_{50}$ value of $843{\mu}g/ml$. Treatments with extract for 24h at $250{\mu}g/ml$ or higher induced cell cycle arrest as indicated by a significant increase of cell population in the G1 phase and a significant decrease in the S phase of the cell cycle. The capability of the aqueous extract to generate radical intermediates was observed at both high pH and near-neutral pH conditions. The findings suggest the antitumor bioactivities of TL against selected breast cancer cells may be due to induction of a G1 cell cycle arrest. Cytotoxicity and cell cycle perturbation that are associated with a high concentration of the extract could be in part explained by the total phenolic contents in the extract and the capacity to generate radical intermediates to modulate cellular proliferative signals.

• 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.