Displaying publications 1 - 20 of 165 in total

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  1. pS2 expression in infiltrating ductal carcinoma of the breast correlates with oestrogen receptor positivity but not with histological grade and lymph node status
    Looi LM, Azura WW, Cheah PL, Ng MH
    Pathology, 2001 Aug;33(3):283-6.
    PMID: 11523925
    This investigation was carried out to gain insight into the prevalence of pS2 expression in invasive ductal breast carcinoma in the Malaysian population and its correlation with oestrogen receptor (ER) protein expression and tumour aggressiveness. Seventy consecutive infiltrating ductal breast carcinomas treated with mastectomy and axillary lymph node clearance were investigated, using the standard avidin-biotin complex immunoperoxidase method with microwave antigen retrieval and commercial monoclonal antibodies (Dako), for expression of pS2 and human ER. This was correlated against histological grade (modified Bloom and Richardson) and the presence of axillary lymph node metastasis of these carcinomas. Four (5.7%) were grade 1, 40 (57.1%) grade 2 and 26 (37.1%) grade 3 tumours. A total of 45 (64%) showed histological evidence of axillary lymph node metastasis. Forty (57%) were ER-positive, while 31 (44%) were pS2-positive. There was a statistically significant correlation between pS2 and ER expressions (chi2-test with Yates correction: P<0.005). There was no correlation between pS2 expression and histological grade (P>0.1) and the presence of lymph node metastasis (P>0.1). Our findings support the views that pS2 may be a co-marker of endocrine responsiveness in invasive breast cancer and that it does not influence breast cancer biology in terms of potential for metastatic spread.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  2. Fulltext p53 Represses the Oncogenic Sno-MiR-28 Derived from a SnoRNA
    Yu F, Bracken CP, Pillman KA, Lawrence DM, Goodall GJ, Callen DF, et al.
    PLoS One, 2015;10(6):e0129190.
    PMID: 26061048 DOI: 10.1371/journal.pone.0129190
    p53 is a master tumour repressor that participates in vast regulatory networks, including feedback loops involving microRNAs (miRNAs) that regulate p53 and that themselves are direct p53 transcriptional targets. We show here that a group of polycistronic miRNA-like non-coding RNAs derived from small nucleolar RNAs (sno-miRNAs) are transcriptionally repressed by p53 through their host gene, SNHG1. The most abundant of these, sno-miR-28, directly targets the p53-stabilizing gene, TAF9B. Collectively, p53, SNHG1, sno-miR-28 and TAF9B form a regulatory loop which affects p53 stability and downstream p53-regulated pathways. In addition, SNHG1, SNORD28 and sno-miR-28 are all significantly upregulated in breast tumours and the overexpression of sno-miR-28 promotes breast epithelial cell proliferation. This research has broadened our knowledge of the crosstalk between small non-coding RNA pathways and roles of sno-miRNAs in p53 regulation.
    Matched MeSH terms: Breast Neoplasms/metabolism
  3. Fulltext miR-200 affects tamoxifen resistance in breast cancer cells through regulation of MYB
    Gao Y, Zhang W, Liu C, Li G
    Sci Rep, 2019 12 11;9(1):18844.
    PMID: 31827114 DOI: 10.1038/s41598-019-54289-6
    Resistance to tamoxifen is a major clinical challenge. Research in recent years has identified epigenetic changes as mediated by dysregulated miRNAs that can possibly play a role in resistance to tamoxifen in breast cancer patients expressing estrogen receptor (ER). We report here elevated levels of EMT markers (vimentin and ZEB1/2) and reduced levels of EMT-regulating miR-200 (miR-200b and miR-200c) in ER-positive breast cancer cells, MCF-7, that were resistant to tamoxifen, in contrast with the naïve parental MCF-7 cells that were sensitive to tamoxifen. Further, we established regulation of c-MYB by miR-200 in our experimental model. C-MYB was up-regulated in tamoxifen resistant cells and its silencing significantly decreased resistance to tamoxifen and the EMT markers. Forced over-expression of miR-200b/c reduced c-MYB whereas reduced expression of miR-200b/c resulted in increased c-MYB We further confirmed the results in other ER-positive breast cancer cells T47D cells where forced over-expression of c-MYB resulted in induction of EMT and significantly increased resistance to tamoxifen. Thus, we identify a novel mechanism of tamoxifen resistance in breast tumor microenvironment that involves miR-200-MYB signaling.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  4. Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/β-catenin pathway
    Hung TH, Hsu SC, Cheng CY, Choo KB, Tseng CP, Chen TC, et al.
    Oncotarget, 2014 Dec 15;5(23):12273-90.
    PMID: 25401518
    Multidrug resistance in cancer cells arises from altered drug permeability of the cell. We previously reported activation of the Wnt pathway in ABCB1-overexpressed human uterus sarcoma drug-resistant MES-SA/Dx5 cells through active β-catenin and associated transactivation activities, and upregulation of Wnt-targeting genes. In this study, Wnt5A was found to be significantly upregulated in MES-SA/Dx5 and MCF7/ADR2 cells, suggesting an important role for the Wnt5A signaling pathway in cancer drug resistance. Higher cAMP response elements and Tcf/Lef transcription activities were shown in the drug-resistant cancer cells. However, expression of Wnt target genes and CRE activities was downregulated in Wnt5A shRNA stably-transfected MES-SA/Dx5 cells. Cell viability of the drug-resistant cancer cells was also reduced by doxorubicin treatment and Wnt5A shRNA transfection, or by Wnt5A depletion. The in vitro data were supported by immunohistochemical analysis of 24 paired breast cancer biopsies obtained pre- and post-chemotherapeutic treatment. Wnt5A, VEGF and/or ABCB1 were significantly overexpressed after treatment, consistent with clinical chemoresistance. Taken together, the Wnt5A signaling pathway was shown to contribute to regulating the drug-resistance protein ABCB1 and β-catenin-related genes in antagonizing the toxic effects of doxorubicin in the MDR cell lines and in clinical breast cancer samples.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  5. Fulltext Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort
    Emaus MJ, Peeters PH, Bakker MF, Overvad K, Tjønneland A, Olsen A, et al.
    Am J Clin Nutr, 2016 Jan;103(1):168-77.
    PMID: 26607934 DOI: 10.3945/ajcn.114.101436
    BACKGROUND: The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor-negative breast cancer risk.

    OBJECTIVE: This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor-defined breast cancer risk.

    DESIGN: A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors.

    RESULTS: After a median follow-up of 11.5 y (IQR: 10.1-12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER-PR-)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5-quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER-PR- breast cancer (ER-PR-: HRquintile 5-quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5-quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor-defined breast cancer risk.

    CONCLUSION: This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk.

    Matched MeSH terms: Breast Neoplasms/metabolism
  6. Fulltext Unmasking Heavily O-Glycosylated Serum Proteins Using Perchloric Acid: Identification of Serum Proteoglycan 4 and Protease C1 Inhibitor as Molecular Indicators for Screening of Breast Cancer
    Lee CS, Taib NA, Ashrafzadeh A, Fadzli F, Harun F, Rahmat K, et al.
    PLoS One, 2016;11(2):e0149551.
    PMID: 26890881 DOI: 10.1371/journal.pone.0149551
    Heavily glycosylated mucin glycopeptides such as CA 27.29 and CA 15-3 are currently being used as biomarkers for detection and monitoring of breast cancer. However, they are not well detected at the early stages of the cancer. In the present study, perchloric acid (PCA) was used to enhance detection of mucin-type O-glycosylated proteins in the serum in an attempt to identify new biomarkers for early stage breast cancer. Sensitivity and specificity of an earlier developed sandwich enzyme-linked lectin assay were significantly improved with the use of serum PCA isolates. When a pilot case-control study was performed using the serum PCA isolates of normal participants (n = 105) and patients with stage 0 (n = 31) and stage I (n = 48) breast cancer, higher levels of total O-glycosylated proteins in sera of both groups of early stage breast cancer patients compared to the normal control women were demonstrated. Further analysis by gel-based proteomics detected significant inverse altered abundance of proteoglycan 4 and plasma protease C1 inhibitor in both the early stages of breast cancer patients compared to the controls. Our data suggests that the ratio of serum proteoglycan 4 to protease C1 inhibitor may be used for screening of early breast cancer although this requires further validation in clinically representative populations.
    Matched MeSH terms: Breast Neoplasms/metabolism
  7. UPLC-QTOF/MS-based phenolic profiling of Melastomaceae, their antioxidant activity and cytotoxic effects against human breast cancer cell MDA-MB-231
    Hamid HA, Ramli ANM, Zamri N, Yusoff MM
    Food Chem, 2018 Nov 01;265:253-259.
    PMID: 29884381 DOI: 10.1016/j.foodchem.2018.05.033
    Eleven compounds were identified during profiling of polyphenols by UPLC-QTOF/MS. In abundance was quercetin-3-O-α-l-arabinofuranoside in M. malabathricum ethanolic leaves extract while 6-hydroxykaempferol-3-O-glucoside was present in the leaves extract of M. decenfidum (its rare variety). TPC and TFC were significantly higher in M. decemfidum extract than M. malabathricum extract. During DPPH, FRAF and β-carotene bleaching assays, M. decemfidum extract exhibited greater antioxidant activity compared to M. malabathricum extract. Effect of M. malabathricum and M. decemfidum extracts on viability of MDA-MB-231 cell at concentrations 6.25-100 μg/mL were evaluated for 24, 48 and 72 h. After 48 and 72 h treatment, M. malabathricum and M. decemfidum leaves extracts exhibited significant activity in inhibiting MDA-MB-231 cancer cell line with M. malabathricum extract being more cytotoxic. M. malabathricum and M. imbricatum serves as potential daily dietary source of natural phenolics and to improve chemotherapeutic effectiveness.
    Matched MeSH terms: Breast Neoplasms/metabolism
  8. Fulltext Two truncating variants in FANCC and breast cancer risk
    Dörk T, Peterlongo P, Mannermaa A, Bolla MK, Wang Q, Dennis J, et al.
    Sci Rep, 2019 08 29;9(1):12524.
    PMID: 31467304 DOI: 10.1038/s41598-019-48804-y
    Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
    Matched MeSH terms: Breast Neoplasms/metabolism
  9. Fulltext Triple negative breast cancer: the role of metabolic pathways
    Dean SJ, Rhodes A
    Malays J Pathol, 2014 Dec;36(3):155-62.
    PMID: 25500513 MyJurnal
    The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.
    Matched MeSH terms: Triple Negative Breast Neoplasms/metabolism*
  10. Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free Quantitative Proteomic Analysis
    Ramdas P, Radhakrishnan AK, Abdu Sani AA, Abdul-Rahman PS
    Nutr Cancer, 2019;71(8):1263-1271.
    PMID: 31084432 DOI: 10.1080/01635581.2019.1607407
    Tocotrienols (T3), a family of vitamin E, are reported to possess potent anti-cancer effects but the molecular mechanisms behind these effects still remain unclear. The aim of this study was to investigate how T3 exert anti-cancer effects on MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were chosen for this study as they are triple-negative and highly metastatic cells, which form aggressive tumors in experimental models. The MDA-MB-231 cells were treated with varying concentrations (0-20 µg mL-1) of gamma (γ) or delta (δ) T3 and the secretome profiles of these cells treated with half maximal inhibitory concentration (IC50) of γT3 (5.8 µg mL-1) or δT3 (4.0 µg mL-1) were determined using label-free quantitative proteomic strategy. A total of 103, 174 and 141 proteins were identified with ProteinLynx Global Server (PLGS) score of more than 200 and above 25% sequence coverage in the untreated control and T3-treated cell culture supernatant respectively. A total of 18 proteins were dysregulated between untreated control and T3 (δT3 or γT3) treated conditions. The results showed that T3 treatment downregulated the exogenous Cathepsin D and Serpine1 proteins but upregulated Profilin-1 protein, which play a key role in breast cancer in the MDA-MB-231 cells. These findings strongly suggest that T3 may induce differential expression of secreted proteins involved in the cytoskeletal regulation of RHO GTPase signaling pathway.
    Matched MeSH terms: Breast Neoplasms/metabolism*; Triple Negative Breast Neoplasms/metabolism*
  11. Fulltext Tocotrienol levels in adipose tissue of benign and malignant breast lumps in patients in Malaysia
    Nesaretnam K, Gomez PA, Selvaduray KR, Razak GA
    Asia Pac J Clin Nutr, 2007;16(3):498-504.
    PMID: 17704032
    Data on dietary exposure to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol (alpha-T) in observational studies have failed to provide consistent support for the idea that alpha-T provides women with any protection from breast cancer. In contrast, studies indicate that alpha, gamma, and delta-tocotrienols but not alpha-T have potent anti-proliferative effects in human breast cancer cells. Our aim was to investigate whether there was a difference in tocopherol and tocotrienol concentrations in malignant and benign adipose tissue, in a Malaysian population consuming predominantly a palm oil diet. The study was undertaken using fatty acid levels in breast adipose tissue as a biomarker of qualitative dietary intake of fatty acids. The major fatty acids in breast adipose tissue of patients (benign and malignant) were oleic acid (45-46%), palmitic (28-29%) and linoleic (11-12%). No differences were evident in the fatty acid composition of the two groups. There was a significant difference (p=0.006) in the total tocotrienol levels between malignant (13.7 +/- 6.0 microg/g) and benign (20+/-6.0 microg/g) adipose tissue samples. However, no significant differences were seen in the total tocopherol levels (p=0.42) in the two groups. The study reveals that dietary intake influences adipose tissue fatty acid levels and that adipose tissue is a dynamic reservoir of fat soluble nutrients. The higher adipose tissue concentrations of tocotrienols in benign patients provide support for the idea that tocotrienols may provide protection against breast cancer.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  12. Fulltext The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells
    Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, et al.
    PLoS One, 2017;12(8):e0182357.
    PMID: 28771532 DOI: 10.1371/journal.pone.0182357
    Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.
    Matched MeSH terms: Triple Negative Breast Neoplasms/metabolism
  13. The kinase LMTK3 promotes invasion in breast cancer through GRB2-mediated induction of integrin β₁
    Xu Y, Zhang H, Lit LC, Grothey A, Athanasiadou M, Kiritsi M, et al.
    Sci Signal, 2014 Jun 17;7(330):ra58.
    PMID: 24939894 DOI: 10.1126/scisignal.2005170
    Lemur tyrosine kinase 3 (LMTK3) is associated with cell proliferation and endocrine resistance in breast cancer. We found that, in cultured breast cancer cell lines, LMTK3 promotes the development of a metastatic phenotype by inducing the expression of genes encoding integrin subunits. Invasive behavior in various breast cancer cell lines positively correlated with the abundance of LMTK3. Overexpression of LMTK3 in a breast cancer cell line with low endogenous LMTK3 abundance promoted actin cytoskeleton remodeling, focal adhesion formation, and adhesion to collagen and fibronectin in culture. Using SILAC (stable isotope labeling by amino acids in cell culture) proteomic analysis, we found that LMTK3 increased the abundance of integrin subunits α5 and β1, encoded by ITGA5 and ITGB1. This effect depended on the CDC42 Rho family guanosine triphosphatase, which was in turn activated by the interaction between LMTK3 and growth factor receptor-bound protein 2 (GRB2), an adaptor protein that mediates receptor tyrosine kinase-induced activation of RAS and downstream signaling. Knockdown of GRB2 suppressed LMTK3-induced CDC42 activation, blocked ITGA5 and ITGB1 expression promoted by the transcription factor serum response factor (SRF), and reduced invasive activity. Furthermore, abundance of LMTK3 positively correlated with that of the integrin β1 subunit in breast cancer patient's tumors. Our findings suggest a role for LMTK3 in promoting integrin activity during breast cancer progression and metastasis.
    Matched MeSH terms: Breast Neoplasms/metabolism
  14. The estrogen receptor negative-progesterone receptor positive breast carcinoma is a biological entity and not a technical artifact
    Ng CH, Pathy NB, Taib NA, Mun KS, Rhodes A, Yip CH
    Asian Pac J Cancer Prev, 2012;13(4):1111-3.
    PMID: 22799290
    The ER-/PR+ breast tumor may be the result of a false ER negative result. The aim of this study was to investigate whether there is a difference in patient and tumor characteristics of the ER-/PR+ phenotype in an Asian setting. A total of 2629 breast cancer patients were categorized on the basis of their age, ethnicity, tumor hormonal receptor phenotype, grade and histological type. There were 1230 (46.8%) ER+/PR+, 306 (11.6%) ER+/PR-, 122 (4.6%) ER-/PR+ and 972 (37%) ER-/PR-. ER-/PR+ tumors were 2.5 times more likely to be younger than 50 years at diagnosis (OR: 2.52; 95% CI: 1.72-3.67). Compared to ER+/PR+ tumors, the ER-/ PR+ phenotype was twice more likely to be associated with grade 3 tumors (OR:2.02; 95%CI: 1.00-4.10). In contrast, compared to ER-/PR- tumors, the ER-/PR+ phenotype was 90% less likely to be associated with a grade 3 tumor (OR: 0.12; 95%CI:0.05-0.26), and more likely to have invasive lobular than invasive ductal histology (OR: 3.66; 95%CI: 1.47-9.11). These results show that the ER-/PR+ phenotype occurs in a younger age group and is associated with intermediate histopathological characteristics compared to ER+/PR+ and ER-/PR- tumors. This may imply that it is a distinct entity and not a technical artifact.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  15. The effects of Naja sumatrana venom cytotoxin, sumaCTX on alteration of the secretome in MCF-7 breast cancer cells following membrane permeabilization
    Hiu JJ, Yap MKK
    Int J Biol Macromol, 2021 Aug 01;184:776-786.
    PMID: 34174307 DOI: 10.1016/j.ijbiomac.2021.06.145
    Naja sumatrana venom cytotoxin (sumaCTX) is a basic protein which belongs to three-finger toxin family. It has been shown to induce caspase-dependent, mitochondrial-mediated apoptosis in MCF-7 cells at lower concentrations. This study aimed to investigate the alteration of secretome in MCF-7 cells following membrane permeabilization by high concentrations of sumaCTX, using label-free quantitative (LFQ) approach. The degree of membrane permeabilization of sumaCTX was determined by lactate dehydrogenase (LDH) assay and calcein-propidium iodide (PI) assays. LDH and calcein-PI assays revealed time-dependent membrane permeabilization within a narrow concentration range. However, as toxin concentrations increased, prolonged exposure of MCF-7 cells to sumaCTX did not promote the progression of membrane permeabilization. The secretome analyses showed that membrane permeabilization was an event preceding the release of intracellular proteins. Bioinformatics analyses of the LFQ secretome revealed the presence of 105 significantly distinguished proteins involved in metabolism, structural supports, inflammatory responses, and necroptosis in MCF-7 cells treated with 29.8 μg/mL of sumaCTX. Necroptosis was presumably an initial stress response in MCF-7 cells when exposed to high sumaCTX concentration. Collectively, sumaCTX-induced the loss of membrane integrity in a concentration-dependent manner, whereby the cell death pattern of MCF-7 cells transformed from apoptosis to necroptosis with increasing toxin concentrations.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  16. Fulltext The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to stage and grade of patients
    Liang S, Singh M, Gam LH
    J Biomed Biotechnol, 2010;2010:516469.
    PMID: 21197096 DOI: 10.1155/2010/516469
    Breast cancer is a leading cause of female deaths worldwide. In Malaysia, it is the most common form of female cancer while Infiltrating ductal carcinoma (IDC) is the most common form of breast cancer. A proteomic approach was used to identify changes in the protein profile of breast cancerous and normal tissues. The patients were divided into different cohorts according to tumour stage and grade. We identified twenty-four differentially expressed hydrophilic proteins. A few proteins were found significantly related to various stages and grades of IDC, amongst which were SEC13-like 1 (isoform b), calreticulin, 14-3-3 protein zeta, and 14-3-3 protein eta. In this study, we found that by defining the expression of the proteins according to stages and grades of IDC, a significant relationship between the expression of the proteins with the stage or grade of IDC can be established, which increases the usefulness of these proteins as biomarkers for IDC.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  17. Fulltext The cytotoxic effect and glucose uptake modulation of Baeckea frutescens on breast cancer cells
    Shahruzaman SH, Mustafa MF, Ramli S, Maniam S, Fakurazi S, Maniam S
    BMC Complement Altern Med, 2019 Aug 19;19(1):220.
    PMID: 31426778 DOI: 10.1186/s12906-019-2628-z
    BACKGROUND: Baeckea frutescens (B. frutescens) of the family Myrtaceae is a plant that has been used in traditional medicine. It is known to have antibacterial, antipyretic and cytoprotective properties. The objective of this study is to explore the mechanism of B. frutescens leaves extracts in eliminating breast cancer cells.

    METHOD: B. frutescens leaves extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxicity of these extracts at various concentrations (20 to 160 μg/ml) were tested using cell viability assay after 24, 48 and 72 h of treatment. The IC50 value in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscope. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening was performed for alkaloids, flavonoids, tannins, triterpenoids, and phenols.

    RESULTS: B. frutescens leaves extracts showed IC50 value ranging from 10 -127μg/ml in MCF-7 cells after 72 h of treatment. Hexane extract had the lowest IC50 value (10μg/ml), indicating its potent selective cytotoxic activity. Morphology of MCF-7 cells after treatment with B. frutescens extracts exhibited evidence of apoptosis that included membrane blebbing and chromatin condensation. In the glucose uptake assay, B. frutescens extracts suppressed glucose uptake in cancer cells as early as 24 h upon treatment. The inhibition was significantly lower compared to the positive control WZB117 at their respective IC50 value after 72 h incubation. It was also shown that the glucose inhibition is selective towards cancer cells compared to normal cells. The phytochemical analysis of the extract using hexane as the solvent in particular gave similar quantities of tannin, triterpenoids, flavonoid and phenols. Presumably, these metabolites have a synergistic effect in the in vitro testing, producing the potent IC50 value and subsequently cell death.

    CONCLUSION: This study reports the potent selective cytotoxic effect of B. frutescens leaves hexane extract against MCF-7 cancer cells. B. frutescens extracts selectively suppressed cancer cells glucose uptake and subsequently induced cancer cell death. These findings suggest a new role of B. frutescens in cancer cell metabolism.

    Matched MeSH terms: Breast Neoplasms/metabolism*
  18. Fulltext The PCA and LDA analysis on the differential expression of proteins in breast cancer
    Liang S, Singh M, Dharmaraj S, Gam LH
    Dis Markers, 2010;29(5):231-42.
    PMID: 21206008 DOI: 10.3233/DMA-2010-0753
    Breast cancer is a leading cause of mortality in women. In Malaysia, it is the most common cancer to affect women. The most common form of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was undertaken to identify protein profile changes between cancerous and normal breast tissues from 18 patients. Two protein extracts; aqueous soluble and membrane associated protein extracts were studied. Thirty four differentially expressed proteins were identified. The intensities of the proteins were used as variables in PCA and reduced data of six principal components (PC) were subjected to LDA in order to evaluate the potential of these proteins as collective biomarkers for breast cancer. The protein intensities of SEC13-like 1 (isoform b) and calreticulin contributed the most to the first PC while the protein intensities of fibrinogen beta chain precursor and ATP synthase D chain contributed the most to the second PC. Transthyretin precursor and apolipoprotein A-1 precursor contributed the most to the third PC. The results of LDA indicated good classification of samples into normal and cancerous types when the first 6 PCs were used as the variables. The percentage of correct classification was 91.7% for the originally grouped tissue samples and 88.9% for cross-validated samples.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  19. Fulltext The Molecular Targets and Anti-Invasive Effects of 2,6-bis-(4-hydroxyl-3methoxybenzylidine) cyclohexanone or BHMC in MDA-MB-231 Human Breast Cancer Cells
    Harun SNA, Israf DA, Tham CL, Lam KW, Cheema MS, Md Hashim NF
    Molecules, 2018 Apr 10;23(4).
    PMID: 29642589 DOI: 10.3390/molecules23040865
    In order to metastasize, tumor cells need to migrate and invade the surrounding tissues. It is important to identify compound(s) capable of disrupting the metastasis of invasive cancer cells, especially for hindering invadopodia formation, so as to provide anti-metastasis targeted therapy. Invadopodia are thought to be specialized actin-rich protrusions formed by highly invasive cancer cells to degrade the extracellular matrix (ECM). A curcuminoid analogue known as 2,6-bis-(4-hydroxy-3-methoxybenzylidine)cyclohexanone or BHMC has shown good potential in inhibiting inflammation and hyperalgesia. It also possesses an anti-tumor effects on 4T1 murine breast cancer cells in vivo. However, there is still a lack of empirical evidence on how BHMC works in preventing human breast cancer invasion. In this study, we investigated the effect of BHMC on MDA-MB-231 breast cancer cells and its underlying mechanism of action to prevent breast cancer invasion, especially during the formation of invadopodia. All MDA-MB-231 cells, which were exposed to the non-cytotoxic concentrations of BHMC, expressed the proliferating cell nuclear antigen (PCNA), which indicate that the anti-proliferative effects of BHMC did not interfere in the subsequent experiments. By using a scratch migration assay, transwell migration and invasion assays, we determined that BHMC reduces the percentage of migration and invasion of MDA-MB-231 cells. The gelatin degradation assay showed that BHMC reduced the number of cells with invadopodia. Analysis of the proteins involved in the invasion showed that there is a significant reduction in the expressions of Rho guanine nucleotide exchange factor 7 (β-PIX), matrix metalloproteinase-9 (MMP-9), and membrane type 1 matrix metalloproteinase (MT1-MMP) in the presence of BHMC treatment at 12.5 µM. Therefore, it can be postulated that BHMC at 12.5 µM is the optimal concentration for preventing breast cancer invasion.
    Matched MeSH terms: Breast Neoplasms/metabolism*
  20. Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: characterization, stability assessment and cytotoxicity
    How CW, Rasedee A, Manickam S, Rosli R
    Colloids Surf B Biointerfaces, 2013 Dec 1;112:393-9.
    PMID: 24036474 DOI: 10.1016/j.colsurfb.2013.08.009
    Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines.
    Matched MeSH terms: Breast Neoplasms/metabolism
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