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Fulltext Modification of MCF-10A cells with pioglitazone and serum-rich growth medium increases soluble factors in the conditioned medium, likely reducing BT-474 cell growth

Khoo BY, Miswan N, Balaram P, Nadarajan K, Elstner E

Int J Mol Sci, 2012;13(5):5607-27.
PMID: 22754319 DOI: 10.3390/ijms13055607

In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or serum-rich growth media, at appropriate concentrations, for 1 week. The MCF-10A cells preincubated with pioglitazone and/or serum-rich growth media were then co-cultured adhesively and non-adhesively with BT-474 cells for another week. Co-culture of BT-474 cells with the preincubated MCF-10A cells, both adhesively and non-adhesively, reduced the growth of the cancer cells. The inhibitory effect of the preincubated MCF-10A cells against the growth of BT-474 cells was likely produced by increasing levels of soluble factors secreted by the preincubated MCF-10A cells into the conditioned medium, as immunoassayed by ELISA. However, only an elevated level of a soluble factor distinguished the conditioned medium collected from the MCF-10A cells preincubated with pioglitazone and serum-rich growth medium than that with pioglitazone alone. This finding was further confirmed by the induction of the soluble factor transcript expression in the preincubated MCF-10A cells, as determined using real-time PCR, for the above phenomenon. Furthermore, modification of the MCF-10A cells through preincubation did not change the morphology of the cells, indicating that the preincubated cells may potentially be injected into mammary fat pads to reduce cancer growth in patients or to be used for others cell-mediated therapy.

Matched MeSH terms: Breast Neoplasms/pathology
Fulltext Does the axillary lymph node ratio have any added prognostic value over pN staging for South East Asian breast cancer patients?

Saxena N, Hartman M, Yip CH, Bhoo-Pathy N, Khin LW, Taib NA, et al.

PLoS One, 2012;7(9):e45809.
PMID: 23029254 DOI: 10.1371/journal.pone.0045809

Lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is reported to be superior to the absolute number of nodes involved (pN stage) in classifying patients at high versus low risk of death following breast cancer. The added prognostic value of LNR over pN in addition to other prognostic factors has never been assessed.

Matched MeSH terms: Breast Neoplasms/pathology*
Fulltext The risk of recurrence in breast cancer patients treated with tamoxifen: polymorphisms of CYP2D6 and ABCB1

Teh LK, Mohamed NI, Salleh MZ, Rohaizak M, Shahrun NS, Saladina JJ, et al.

AAPS J, 2012 Mar;14(1):52-9.
PMID: 22183189 DOI: 10.1208/s12248-011-9313-6

CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.

Matched MeSH terms: Breast Neoplasms/pathology
Genetic polymorphisms of TP53-binding protein 1 (TP53BP1) gene and association with breast cancer risk

Naidu R, Har YC, Taib NA

APMIS, 2011 Jul;119(7):460-7.
PMID: 21635553 DOI: 10.1111/j.1600-0463.2011.02753.x

In the present study, we evaluated the association between the TP53BP1 Glu353Asp and T-885G polymorphisms and breast cancer risk as well as with the clinicopathological characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using PCR-RFLP method in a hospital-based Malaysian population. Breast cancer risk was not observed among women who were heterozygous (OR(adj) = 0.887; 95% CI, 0.632-1.245) or homozygous (OR(adj) = 1.083; 95% CI, 0.595-1.969) for Asp allele, and those carriers of Asp allele (OR(adj) = 0.979; 95% CI, 0.771-1.243). Similarly, women who were TG heterozygotes (OR(adj) = 1.181; 95% CI, 0.842-1.658) or GG homozygotes (OR(adj) = 1.362; 95% CI, 0.746-2.486) and carriers of G allele (OR(adj) = 1.147; 95% CI, 0.903-1.458) were not associated with increased risk of breast cancer. Asp allele genotype was significantly associated with ER negativity (p = 0.0015) and poorly differentiated tumours (p = 0.008), but G allele genotype was not associated with the clinicopathological characteristics. In conclusion, Glu353Asp and T-885G polymorphic variants might not have an influence on breast cancer risk, thus might not be potential candidates for cancer susceptibility. Glu353Asp variant might be associated with tumour aggressiveness as defined by its association with ER negativity and poorly differentiated tumours.

Matched MeSH terms: Breast Neoplasms/pathology
Generation and characterization of a high-affinity monoclonal antibody for MUC1 measurement in breast cancer

Hamid SS, Cheah SH

Hybridoma (Larchmt), 2011 Apr;30(2):137-43.
PMID: 21529286 DOI: 10.1089/hyb.2010.0091

Breast mucin is secreted by breast tumor cells and serves as a marker for breast cancer. Thus, antibodies against breast mucin will be valuable in the development of immunotherapy and laboratory diagnostic tests. Monoclonal antibodies (MAbs) against breast cancer-associated antigen were generated and characterized. Balb/c mice were immunized with breast cancer-associated antigen CA15-3, and subsequently splenocytes from immunized mice were fused with myeloma cells. After fusion, culture supernatants from hybridomas surviving HAT medium were screened by enzyme-linked immunosorbent assay (ELISA). A total of eight hybridomas producing MAbs against breast cancer showed significant levels of antibody activity against CA15-3. Two selected stable hybridomas were adapted into CELLine CL 350 bioreactors, and the MAbs produced were characterized for their subclass, specificity, and affinity. The MAbs were of high specificity and affinity as shown by ELISA. The MAbs produced may represent a powerful tool and are considered promising reagents for use in diagnosis and detection of early stage of the disease.

Matched MeSH terms: Breast Neoplasms/pathology
Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women

Looi LM, Cheah PL, Ng MH, Yip CH, Mun KS, Rahman NA

Asian Pac J Cancer Prev, 2010;11(3):713-6.
PMID: 21039041

A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.

Matched MeSH terms: Breast Neoplasms/pathology*
Fulltext Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro

Yaacob NS, Hamzah N, Nik Mohamed Kamal NN, Zainal Abidin SA, Lai CS, Navaratnam V, et al.

BMC Complement Altern Med, 2010;10:42.
PMID: 20684795 DOI: 10.1186/1472-6882-10-42

The leaves of Strobilanthes crispus (S. crispus) which is native to the regions of Madagascar to the Malay Archipelago, are used in folk medicine for their antidiabetic, diuretic, anticancer and blood pressure lowering properties. Crude extracts of this plant have been found to be cytotoxic to human cancer cell lines and protective against chemically-induced hepatocarcinogenesis in rats. In this study, the cytotoxicity of various sub-fractions of dichloromethane extract isolated from the leaves of S. crispus was determined and the anticancer activity of one of the bioactive sub-fractions, SC/D-F9, was further analysed in breast and prostate cancer cell lines.

Matched MeSH terms: Breast Neoplasms/pathology
Fulltext Characterisation of the binding properties of Bacillus thuringiensis 18 toxin on leukaemic cells

Wong RS, Mohamed SM, Nadarajah VD, Tengku IA

J Exp Clin Cancer Res, 2010;29:86.
PMID: 20591169 DOI: 10.1186/1756-9966-29-86

Various strains of Bacillus thuringiensis (Bt) have been found to produce parasporal proteins that are cytotoxic to human cancer cells. This study aims to establish the binding affinity of purified Bt 18 toxin for CEM-SS (T lymphoblastic leukaemia cell line), to determine if competition exists between the toxin and commercial anticancer drugs for the binding site on CEM-SS and to localise the binding site of the toxin on CEM-SS.

Matched MeSH terms: Breast Neoplasms/pathology
Factors associated with HER2 overexpression in breast cancer: Experience in an Asian developing country

Tan GH, Choo WY, Taib NA, Yip CH

Asian Pac J Cancer Prev, 2009;10(5):837-40.
PMID: 20104975

INTRODUCTION: The HER2 gene is amplified in up to 30% of human breast cancers, leading to overexpression of the HER2 protein on the cell surface. Overexpression of HER2 is associated with a more aggressive cancer and hence a poorer overall survival.
OBJECTIVE: To evaluate the association between clinico-pathological features and HER2 overexpression in breast cancer.
METHODS: This is a retrospective study conducted in the Department of Surgery, University Malaya Medical Centre. The association between HER2 overexpression, determined by immunohistochemistry, and other clinicopathological factors was evaluated in 996 patients with newly diagnosed breast cancer treated from 2005 to 2007 using univariate and multivariate logistic regression.
RESULTS: HER2 overexpression occurred in 30.3% of patients. On bivariate analysis, HER2 overexpression was inversely related to ER expression (p<0.01) and PR expression (p<0.01). This overexpression was associated with a higher tumour grade, lymphovascular positivity and infiltrating ductal carcinoma subtype. On multivariate analysis, HER2 overexpression was significantly associated with higher tumour grade (p= 0.018, CI 1.25-11.04), PR negativity (p= 0.002, CI 0.30-0.77) and lymphovascular positivity (p= 0.042, CI 1.01-2.12).
CONCLUSIONS: HER2 overexpression was observed in 30.3% of Malaysian female breast cancer patients. This group of patients represents a more aggressive subtype of breast cancer with higher tumour grade, PR negativity and lymphovascular positivity. No significant relationship was established between HER2 overexpression and age, race, lymph node, ER, pathology subtype and stage of disease from this study.

Matched MeSH terms: Breast Neoplasms/pathology
Fulltext Mutant p53 mediates survival of breast cancer cells

Lim LY, Vidnovic N, Ellisen LW, Leong CO

Br. J. Cancer, 2009 Nov 3;101(9):1606-12.
PMID: 19773755 DOI: 10.1038/sj.bjc.6605335

p53 is the most commonly mutated tumour-suppressor gene in human cancers. Unlike other tumour-suppressor genes, most p53 cancer mutations are missense mutations within the core domain, leading to the expression of a full-length mutant p53 protein. Accumulating evidence has indicated that p53 cancer mutants not only lose tumour suppression activity but also gain new oncogenic activities to promote tumourigenesis.

Matched MeSH terms: Breast Neoplasms/pathology*
Fulltext E-cadherin expression correlates with histologic type but not tumour grade in invasive breast cancer

Nurismah MI, Noriah O, Suryati MY, Sharifah NA

Asian Pac J Cancer Prev, 2008 Oct-Dec;9(4):699-702.
PMID: 19256762

The traditional classification of infiltrating breast carcinomas into ductal and lobular can be diagnostically challenging in a small proportion of cases with equivocal histological features and in in-situ lesions with overlapping features. Distinguishing between the infiltrating ductal (IDC) and lobular (ILC) carcinomas is clinically important because of the different pattern of systemic metastases and prognostic evaluation. E-cadherin is a potentially useful immunohistochemical marker which may serve to differentiate between the two tumour types. We therefore studied E-cadherin expression in 32 cases of breast carcinomas comprising 16 IDCs and 16 ILCs. The correlation between E-cadherin expression and the histological grade of IDCs was also analysed. Our results showed complete loss of E-cadherin expression in all ILCs, while the IDCs consistently showed variable E-cadherin positivity. No significant correlation was found between E- cadherin expression and the histological grade of IDCs. We conclude from this study that E-cadherin is a useful marker to differentiate between IDC and ILC of the breast. A larger study of IDCs is now needed to further evaluate the correlation between E-cadherin and tumour grade to estimate its prognostic potential.

Matched MeSH terms: Breast Neoplasms/pathology*
Fulltext Does the pre-operative value of serum CA15-3 correlate with survival in breast cancer?

Velaiutham S, Taib NA, Ng KL, Yoong BK, Yip CH

Asian Pac J Cancer Prev, 2008 Jul-Sep;9(3):445-8.
PMID: 18990019

INTRODUCTION: CA15-3 is a well-known tumour marker for breast cancer. Currently it is not recommended for screening or diagnosis of breast cancer and its main application is in monitoring response to treatment in women with metastatic breast cancer. The aim of this study was to correlate serum CA15-3 at presentation with the stage of disease and overall survival in women with breast cancer in the University Malaya Medical Centre.

METHODS: This is a retrospective study of 437 women who had CA15-3 levels determined at initial presentation of breast cancer to UMMC between Jan 1999 and Oct 2003.

RESULTS: Of those patients who were adequately staged, CA15-3 was found to be elevated (defined as >51 U/ml) in 0% of Stage 1, 7.9% of Stage 2, 36.7% of Stage 3 and 68.6% of Stage 4 cases. In a subset of 331 patients with survival data, patients with normal CA15-3 had a 85% five year overall survival rate compared to 38% in their counterparts with elevation of the tumor marker. The level of elevation was also significantly related to survival; patients with values more than 200 U/ml exhibited only a 28% five year survival. The association of elevated CA15-3 at initial presentation with poor outcome was maintained over univariate and multivariate analyses.

CONCLUSION: Estimation of CA15-3 at presentation of breast cancer is important as it is an independent prognostic indicator and may prompt the physician to investigate for metastases if elevated.

Matched MeSH terms: Breast Neoplasms/pathology*
Fulltext Immediate breast reconstruction after mastectomy--why do women choose this option?

Shameem H, Yip CH, Fong E

Asian Pac J Cancer Prev, 2008 Jul-Sep;9(3):409-12.
PMID: 18990011

INTRODUCTION: Mastectomy is an essential but disfiguring operation in cancer treatment. The negative impact on body image can however be prevented by immediate reconstruction.
AIM: The aim of this study was to determine the reasons why patients choose to have or not to have immediate breast reconstruction.
METHODOLOGY: This is a cross sectional descriptive study of breast cancer patients post-mastectomy who had and had not undergone immediate breast reconstruction. The patients were asked a series of questions to ascertain the reasons why they chose or did not choose immediate breast reconstruction.
RESULTS: 136 patients in total were interviewed of which 23 had undergone immediate breast reconstruction. 36.8% of the patients had been offered reconstruction. In the non-reconstructed group, the main reason for not having reconstruction were fear of additional surgery. In the group that had reconstruction done, the main reason was to feel whole again. Low on the list were reasons such as trying to improve marital or sexual relations.
CONCLUSION: Only a third of patients undergoing mastectomy were offered immediate reconstruction. In public hospitals in developing countries, limited operating time and availability of plastic surgery services are major barriers to more women being offered the option.

Matched MeSH terms: Breast Neoplasms/pathology
Breast cancer in Sabah, Malaysia: a two year prospective study

Leong BD, Chuah JA, Kumar VM, Yip CH

Asian Pac J Cancer Prev, 2007 Oct-Dec;8(4):525-9.
PMID: 18260722

INTRODUCTION: Malaysian women have a 1 in 20 chance of developing breast cancer in their lifetime. Sabah, formerly known as North Borneo, is part of East Malaysia with a population of 3.39 million and more than 30 ethnic groups. We conducted a 2 year prospective epidemiological study to provide unreported data of breast cancer from this part of the world and to recognise which particular group of patients are more likely to present with advanced disease.

METHODS: All newly diagnosed breast cancers seen at the Queen Elizabeth Hospital, Kota Kinabalu, from January 2005 to December 2006 were included in the study. Patient and tumour characteristics, including age, race, education, socioeconomic background, parity, practice of breast feeding, hormonal medication intake, menopausal status, family history, mode of presentation, histology, grade, stage of disease and hormonal receptors status were collected and analysed.

RESULTS: A total of 186 patients were seen. The commonest age group was 40 to 49 years old (32.3%). Chinese was the commonest race (30.6%) followed by Kadazan-Dusun (24.2%). The commonest histology was invasive ductal carcinoma (88.4%). Stages at presentation were Stage 0- 4.8%, Stage I- 12.9%, Stage II- 30.1%, Stage III- 36.6% and Stage IV- 15.6%. The estrogen and progesterone receptor status was positive in 59.1% and 54.8% of cases, respectively. 73.7% of Chinese patients presented with early cancer compared to 36.4% of the other races. Patients who presented with advanced disease were also poor, non-educated and from rural areas. 20.4% of patients defaulted treatment; most of them opted for traditional alternatives.

CONCLUSIONS: Sabahan women with breast cancer present late. Great efforts are needed to improve public awareness of breast cancer, especially among those who have higher risk of presenting with advanced disease.

Matched MeSH terms: Breast Neoplasms/pathology
Minichromosome maintenance protein 2 is a reliable proliferative marker in breast carcinoma

Reena RM, Mastura M, Siti-Aishah MA, Munirah MA, Norlia A, Naqiyah I, et al.

Ann Diagn Pathol, 2008 Oct;12(5):340-3.
PMID: 18774496 DOI: 10.1016/j.anndiagpath.2008.04.001

This is a study aimed to examine the distribution pattern of a specific minichromosome maintenance protein 2 (MCM2) in benign and malignant breast tissue. We also aim to correlate the frequency of expression of MCM2 with the degree of tumor differentiation. We used immunohistochemistry to examine the distribution and expression pattern of MCM2 on formalin-fixed paraffin-embedded tissue sections of benign (n = 30) and malignant breast tissue (n = 70) (IDC 56, DCIS 4, ILC 2, nonductal 4, mixed type 4). We quantified MCM2 expression by calculating a labeling index, which represents the percentage of epithelial nuclei that stained positively. Immunoreactivity was heterogenous in all the 70 malignant cases examined. Epithelial cells in cycle are most frequent at the tumor periphery. Labeling index of MCM2 was greatest in grade 3 (poorly differentiated) and lowest in grade 1 tumors (well differentiated). Minichromosome maintenance protein 2 expression in breast cancer showed a positive association with histologic grade (P < .05). In all the benign breast tissue examined, no proliferating compartments could be characterized. Minichromosome maintenance protein 2 is a useful proliferative marker of breast carcinoma. The frequency of expression of MCM2 showed an inverse correlation with the degree of tumor differentiation.

Matched MeSH terms: Breast Neoplasms/pathology
Fulltext CD44 expression and axillary lymph node metastasis in infiltrating ductal carcinoma of the breast

Looi LM, Cheah PL, Zhao W, Ng MH, Yip CH

Malays J Pathol, 2006 Dec;28(2):83-6.
PMID: 18376796 MyJurnal

Metastasising ability connotes one of the most important life-threatening properties of malignant neoplasms. Recent studies indicate that CD44 proteins, multifunctional cell adhesion molecules which contribute to "homing" of lymphocytes to lymph nodes as well as cell-cell and cell-matrix interactions, are potential markers of tumour progression. However, whether CD44 expression by human tumours contribute to increased metastatic risk remains controversial. In an attempt to clarify its role in breast cancer, we have investigated the correlation between CD44 expression by breast carcinoma and the presence of axillary lymph node metastases. CD44 expression was detected using a standard immunoperoxidase method on formalin-fixed, paraffin-embedded, primary infiltrating ductal breast carcinoma tissues taken from 60 female patients who underwent mastectomy with axillary node clearance. Tumours were graded according to the modified Bloom and Richardson criteria. 62% of patients had histologically-proven lymph node metastasis. 40% of primary cancers exhibited cytoplasmic membrane immunopositivity for CD44. 46% of primary tumours which have metastasied to axillary lymph nodes were CD44 positive whereas 30% of tumours which have not metastasised expressed CD44. CD44 positivity was expressed by 20% of grade 1, 31% grade 2 and 58% grade 3 tumours. Our results suggest that CD44 may have a role in the progression of breast cancer and emphasise the need to investigate its interaction with other mechanisms of cancer advancement.

Matched MeSH terms: Breast Neoplasms/pathology
Metastatic mucinous carcinoma of the eyelid

Kaur G, Ismail R, Harun H

Malays J Pathol, 2005 Dec;27(2):117-8.
PMID: 17191395

Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.

Matched MeSH terms: Breast Neoplasms/pathology*
Apoptosis induction, cell cycle arrest and in vitro anticancer activity of gonothalamin in a cancer cell lines

Alabsi AM, Ali R, Ali AM, Al-Dubai SA, Harun H, Abu Kasim NH, et al.

Asian Pac J Cancer Prev, 2012;13(10):5131-6.
PMID: 23244123

Cancer is one of the major health problems worldwide and its current treatments have a number of undesired adverse side effects. Natural compounds may reduce these. Currently, a few plant products are being used to treat cancer. In this study, goniothalamin, a natural occurring styryl-lactone extracted from Goniothalamus macrophyllus, was investigated for cytotoxic properties against cervical cancer (HeLa), breast carcinoma (MCF-7) and colon cancer (HT29) cells as well as normal mouse fibroblast (3T3) using MTT assay. Fluorescence microscopy showed that GTN is able to induce apoptosis in HeLa cells in a time dependent manner. Flow cytometry further revealed HeLa cells treated with GTN to be arrested in the S phase. Phosphatidyl serine properties present during apoptosis enable early detection of the apoptosis in the cells. Using annexin V/PI double staining it could be shown that GTN induces early apoptosis on HeLa cells after 24, 48 and 72 h. It could be concluded that goniothalamin showing a promising cytotoxicity effect against several cancer cell lines including cervical cancer cells (HeLa) with apoptosis as the mode of cell death induced on HeLa cells by Goniothalamin was.

Matched MeSH terms: Breast Neoplasms/pathology
Tocotrienol-rich fraction from palm oil affects gene expression in tumors resulting from MCF-7 cell inoculation in athymic mice

Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Reimann K, Razak G, et al.

Lipids, 2004 May;39(5):459-67.
PMID: 15506241

It has recently been shown that tocotrienols are the components of vitamin E responsible for inhibiting the growth of human breast cancer cells in vitro, through an estrogen-independent mechanism. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. To investigate the molecular basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset, incidence, and size of the tumors in nude mice supplemented with TRF compared with the controls. At autopsy, the tumor tissue was excised and analyzed for gene expression by means of a cDNA array technique. Thirty out of 1176 genes were significantly affected. Ten genes were downregulated and 20 genes up-regulated with respect to untreated animals, and some genes in particular were involved in regulating the immune system and its function. The expression of the interferon-inducible transmembrane protein-1 gene was significantly up-regulated in tumors excised from TRF-treated animals compared with control mice. Within the group of genes related to the immune system, we also found that the CD59 glycoprotein precursor gene was up-regulated. Among the functional class of intracellular transducers/effectors/modulators, the c-myc gene was significantly down-regulated in tumors by TRF treatment. Our observations indicate that TRF supplementation significantly and specifically affects MCF-7 cell response after tumor formation in vivo and therefore the host immune function. The observed effect on gene expression is possibly exerted independently from the antioxidant activity typical of this family of molecules.

Matched MeSH terms: Breast Neoplasms/pathology*
Phytochemistry and preliminary biological evaluation of Cyathostemma argenteum, a malaysian plant used traditionally for the treatment of breast cancer

Khamis S, Bibby MC, Brown JE, Cooper PA, Scowen I, Wright CW

Phytother Res, 2004 Jul;18(7):507-10.
PMID: 15305306

Bioassay guided fractionation of the roots of Cyathostemma argenteum using the brine shrimp resulted in the isolation of two uncommon flavanones, 2,5-dihydroxy-7-methoxy flavanone 1 and 2,5-dihydroxy-6,7-dimethoxy flavanone 2 while the stem bark yielded the related compounds 5-hydroxy-7-methoxy flavone 3 and 5-hydroxy-6,7-dimethoxy flavone 4. The alkaloids liriodenine 5 and discretamine 6 as well as benzyl benzoate 7 were isolated from the roots and 6 was also isolated from the stembark. In cytotoxicity tests using four human breast cancer cell lines, 1 and 2 were weakly toxic to MCF-7 cells (IC(50) = 19.6 and 19.0 microM, respectively) but showed little activity against MCF-7 cells resistant to doxorubicin or against two oestrogen receptor-deficient cell lines. Compound 5, but not 6 and 7, was moderately cytotoxic against all four cell lines. These results are discussed in the context of the traditional use of C. argenteum in the treatment of breast cancer.

Matched MeSH terms: Breast Neoplasms/pathology

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