Displaying publications 41 - 60 of 60 in total

Abstract:
Sort:
  1. Yaacob NS, Nik Mohamed Kamal NN, Wong KK, Norazmi MN
    Asian Pac J Cancer Prev, 2015;16(18):8135-40.
    PMID: 26745050
    BACKGROUND: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells.

    MATERIALS AND METHODS: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle- related transcripts was analysed based on a previous microarray dataset.

    RESULTS: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of ERα protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied.

    CONCLUSIONS: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.

    Matched MeSH terms: Tamoxifen/pharmacology*
  2. Nesaretnam K, Dorasamy S, Darbre PD
    Int J Food Sci Nutr, 2000;51 Suppl:S95-103.
    PMID: 11271861
    The vitamin E component of palm oil provides a rich source of tocotrienols which have been shown previously to be growth inhibitory to two human breast cancer cell lines: responsive MCF7 cells and unresponsive MDA-MB-231 cells. Data presented here shows that the tocotrienol-rich fraction (TRF) of palm oil and individual fractions (alpha, gamma and delta) can also inhibit the growth of another responsive human breast cancer cell line, ZR-75-1. At low concentrations in the absence of oestrogen tocotrienols stimulated growth of the ZR-75-1 cells, but at higher concentrations in the presence as well as in the absence of oestradiol, tocotrienols inhibited cell growth strongly. As for MCF7 cells, alpha-tocopherol had no effect on growth of the ZR-75-1 cells in either the absence or presence of oestradiol. In studying the effects of tocotrienols in combination with antioestrogens, it was found that TRF could further inhibit growth of ZR-75-1 cells in the presence of tamoxifen (10(-7) M and 10(-8) M). Individual tocotrienol fractions (alpha, gamma, delta) could inhibit growth of ZR-75-1 cells in the presence of 10(-8) M oestradiol and 10(-8) M pure antioestrogen ICI 164,384. The immature mouse uterine weight bioassay confirmed that TRF could not exert oestrogen antagonist action in vivo. These results provide evidence of wider growth-inhibitory effects of tocotrienols beyond MCF7 and MDA-MB-231 cells, and with an oestrogen-independent mechanism of action, suggest a possible clinical advantage in combining administration of tocotrienols with antioestrogen therapy.
    Matched MeSH terms: Tamoxifen/pharmacology
  3. Pihie AH, Stanslas J, Din LB
    Anticancer Res, 1998 May-Jun;18(3A):1739-43.
    PMID: 9673398
    The antiproliferative activity of a styrylpyrone derivative (SPD) plant extract, was studied in three different human breast cancer cell lines in culture, and was compared with tamoxifen. The number of living cells was evaluated by Methylene Blue staining technique. SPD showed strong antiproliferative activity in estrogen receptor (ER) and progestin receptor (PgR) positive MCF-7 cells (EC50 = 6.30 x 10(-7) M) and receptor-negative MDA-MB-231 (EC50 = 5.62 x 10(-7) M), but it partially inhibited the high progestin receptor positive T47D cells (EC50 = 1.58 x 10(-6) M). Whereas tamoxifen, a nonsteroidal antiestrogen exhibited strong inhibition on MCF-7 cells (EC50 = 1.41 x 10(-6) M) and partial inhibition on T47D cells (EC50 = 2.5 x 10(-6) M), but did not affect the MDA-MB-231 cells in the concentration range 0.1 nM-1 microM (EC50 = 5.01 microM). At the same concentration range SPD and tamoxifen did not inhibit the proliferation of normal human liver cell line CCL 13 and normal bovine kidney MDBK; whereas adriamycin, a common chemotherapy drug for the treatment of advance cancer, caused 95% inhibition at 10(-6) M. Competitive binding studies showed SPD had no ability to inhibit the binding of [3H]estradiol and [3H]progesterone to ER and PgR, respectively but, tamoxifen exhibited affinity for ER. Therefore, it can be concluded that the antiproliferative activity of SPD was selective towards breast cancer cell lines and not mediated by ER or PgR.
    Matched MeSH terms: Tamoxifen/toxicity
  4. 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: Tamoxifen/therapeutic use*
  5. Choo SB, Saifulbahri A, Zullkifli SN, Fadzil ML, Redzuan AM, Abdullah N, et al.
    Climacteric, 2019 04;22(2):175-181.
    PMID: 30556740 DOI: 10.1080/13697137.2018.1540563
    OBJECTIVE: This study was conducted to determine the prevalence and severity of menopausal symptoms and their associated risk factors among postmenopausal breast cancer patients receiving adjuvant endocrine therapy.

    METHODS: Postmenopausal breast cancer patients on endocrine therapy were recruited at three hospitals in Malaysia. Presence and severity of menopausal symptoms were determined using the Menopause Rating Scale. Sociodemographic and clinical data were collected from medical records.

    RESULTS: A total of 192 patients participated in this study. Commonly reported symptoms were musculoskeletal pain (59.9%), physical and mental exhaustion (59.4%), and hot flushes (41.1%). Multivariate analyses indicated that increasing number of years after menopause until the start of endocrine therapy was significantly associated with less likelihood of reporting menopausal symptoms and musculoskeletal pain. Patients with primary or secondary education levels reported significantly less menopausal urogenital symptoms compared to patients with a tertiary education level. Patients using aromatase inhibitors were twice as likely to experience musculoskeletal pain compared to patients using tamoxifen (odds ratio, 2.18; 95% confidence interval, 1.06-4.50; p 

    Matched MeSH terms: Tamoxifen/adverse effects
  6. Huq AM, Wai LK, Rullah K, Mohd Aluwi MFF, Stanslas J, Jamal JA
    Chem Biol Drug Des, 2019 03;93(3):222-231.
    PMID: 30251480 DOI: 10.1111/cbdd.13404
    Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson-Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1 μM) and PGR (13.9-fold at 0.01 μM) genes. ERα-mimosine binding energy was -49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.
    Matched MeSH terms: Tamoxifen/pharmacology
  7. Raihan J, Ahmad U, Yong YK, Eshak Z, Othman F, Ideris A
    BMC Cancer, 2019 Apr 04;19(1):315.
    PMID: 30947706 DOI: 10.1186/s12885-019-5516-5
    BACKGROUND: Different strains of Newcastle disease virus (NDV) worldwide proved to have tumouricidal activity in several types of cancer cells. However, the possible anti-cancer activity of Malaysian NDV AF2240 strain and its mechanism of action remains unknown. The ability of cytokine-related apoptosis-inducing NDV AF2240 to treat breast cancer was investigated in the current study.

    METHODS: A total of 90 mice were used and divided into 15 groups, each group comprising of 6 mice. Tumour, body weight and mortality of the mice were determined throughout the experiment, to observe the effect of NDV and NDV + tamoxifen treatments on the mice. In addition, the toxic effect of the treatments was determined through liver function test. In order to elucidate the involvement of cytokine production induced by NDV, a total of six cytokines, i.e. IL-6, IFN-γ, MCP-1, IL-10, IL12p70 and TNF-α were measured using cytometric bead array assay (plasma) and enzyme-linked immunosorbent spot (isolated splenocytes).

    RESULTS: The results demonstrated that 4 T1 breast cancer cells in allotransplanted mice treated with AF2240 showed a noticeable inhibition of tumour growth and induce apoptotic-related cytokines.

    CONCLUSIONS: NDV AF2240 suppression of breast tumour growth is associated with induction of apoptotic-related cytokines. It would be important to further investigate the molecular mechanism underlaying cytokines production by Newcastle disease virus.

    Matched MeSH terms: Tamoxifen/therapeutic use
  8. Redhwan, A.A., Md Idris, M.N., Zaleha, M.I., Robert, C., Fuad, I., Sami, R.A.
    MyJurnal
    Introduction : The purpose of this study was to determine the quality of life (QOL) of breast cancer survivors based on socio-demographic and clinical characteristics.
    Methods : A cross-sectional study was performed on 125 breast cancer survivors from the outpatient clinics. FACT-B (Functional Assessment of Cancer Therapy-Breast) questionnaire was used to assess survivors’ QOL.
    Results : Survivors with low body mass index (BMI) (underweight) were found to have the lowest overall QOL. Those who were overweight had a higher overall QOL, and those who were normal-weight had the highest QOL. Low educational level, being underweight and low monthly household income were significantly associated with lower overall QOL Tamoxifen use and employment status were significantly associated with QOL in some domains. Time since diagnosis to QOL interview was significantly associated with greater scores in emotional well-being (EWB). Multiple linear regression indicated that age, marital status, monthly household income, surgery and histological grade were indicative of the patients QOL.
    Conclusion : The four primary factors related to better QOL were high educational level, high income, normal body weight and greater duration from the time of diagnosis to the time of interview. Age, marital status, income, lumpectomy and histological grade were indicative of the patient QOL.
    Study site: Oncology and Surgical clinics; Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Tamoxifen
  9. Thang LY, Breadmore MC, See HH
    J Chromatogr A, 2016 Jul 27.
    PMID: 27485148 DOI: 10.1016/j.chroma.2016.07.067
    An online preconcentration method, namely electrokinetic supercharging (EKS), was evaluated for the determination of tamoxifen and its metabolites in human plasma in nonaqueous capillary electrophoresis with ultraviolet detection (NACE-UV). This method was comprehensively optimized in terms of the leading electrolyte (LE) and terminating electrolyte (TE) injection lengths, as well as electrokinetic sample injection time. The optimized EKS conditions employed were as follows: hydrodynamic injection (HI) of 10mM potassium chloride as LE at 150mbar for 36s (4% of total capillary volume). The sample was injected at 10kV for 300s, followed by HI of 10mM pimozide as TE at 150mbar for 36s (4% of total capillary volume). Separation was performed in 7.5mM deoxycholic acid sodium salt, 15mM acetic acid and 1mM 18-crown-6 in 100% methanol at +25kV with UV detection at 205nm. Under optimized conditions, the sensitivity was enhanced between 160- and 600-fold when compared with our previously developed method based on HI at 150mbar for 12s. The detection limit of the method for tamoxifen and its metabolites were 0.05-0.25ng/mL, with RSDs between 2.1% and 3.5%. Recoveries in spiked human plasma were 95.6%-99.7%. A comparison was also made between the proposed EKS approach and the standard field-amplified sample injection (FASI) technique. EKS proved to be 3-5 times more sensitive than the FASI. The new EKS method was applied to the analysis of tamoxifen and its metabolites in plasma samples from breast cancer patients after liquid-liquid extraction.
    Matched MeSH terms: Tamoxifen
  10. Amin, I.M., Sheikh Abdul Kadir, S.H., Isa, M.R., Rosdy. N.M.M.N.M., Hasani NAH
    JUMMEC, 2016;19(1):1-10.
    MyJurnal
    The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as many
    of the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted from
    the leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breast
    cancer cells (MCF-7), but not to ERa-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF-
    10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response of
    MCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen alone
    or a combination of emodin and tamoxifen, at their respective IC50 concentrations and at different time points
    of 24 hours, 48 hours and 72 hours. The respective IC50s were the concentrations of aloe emodin and tamoxifen
    required to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined using
    trypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genes
    of MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data was
    evaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity of
    tamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide a
    rational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifen
    on the viability of ERa-positive-breast cancer cells.
    Matched MeSH terms: Tamoxifen
  11. Kakkar S, Kumar S, Lim SM, Ramasamy K, Mani V, Shah SAA, et al.
    Chem Cent J, 2018 Dec 04;12(1):130.
    PMID: 30515643 DOI: 10.1186/s13065-018-0499-x
    BACKGROUND: In view of wide range of biological activities of oxazole, a new series of oxazole analogues was synthesized and its chemical structures were confirmed by spectral data (Proton/Carbon-NMR, IR, MS etc.). The synthesized oxazole derivatives were screened for their antimicrobial and antiproliferative activities.

    RESULTS AND DISCUSSION: The antimicrobial activity was performed against selected fungal and bacterial strains using tube dilution method. The antiproliferative potential was evaluated against human colorectal carcinoma (HCT116) and oestrogen- positive human breast carcinoma (MCF7) cancer cell lines using Sulforhodamine B assay and, results were compared to standard drugs, 5-fluorouracil and tamoxifen, respectively.

    CONCLUSION: The performed antimicrobial activity indicated that compounds 3, 5, 6, 8 and 14 showed promising activity against selected microbial species. Antiproliferative screening found compound 14 to be the most potent compound against HCT116 (IC50 = 71.8 µM), whereas Compound 6 was the most potent against MCF7 (IC50 = 74.1 µM). Further, the molecular docking study has been carried to find out the interaction between active oxazole compounds with CDK8 (HCT116) and ER-α (MCF7) proteins indicated that compound 14 and 6 showed good dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

    Matched MeSH terms: Tamoxifen
  12. Tan WN, Lim JQ, Afiqah F, Nik Mohamed Kamal NNS, Abdul Aziz FA, Tong WY, et al.
    Nat Prod Res, 2018 Apr;32(7):854-858.
    PMID: 28782393 DOI: 10.1080/14786419.2017.1361951
    Garcinia atroviridis Griff. ex T. Anders. is used as a medication agent in folkloric medicine. The present study was to examine the chemical composition of the stem bark and leaf of G. atroviridis as well as their cytotoxic effects against MCF-7 cells. The constituents obtained by hydrodistillation were identified using GC-MS. The stem bark oil (EO-SB) composed mainly the palmitoleic acid (51.9%) and palmitic acid (21.9%), while the leaf oil (EO-L) was dominated by (E)-β-farnesene (58.5%) and β-caryophyllene (16.9%). Treatment of MCF-7 cells using EO-L (100 μg/mL) caused more than 50% cell death while EO-SB did not induce cytotoxic effect. EO-L has stimulated the growth of BEAS-2B normal cells, but not in MCF-7 cancerous cells. The IC50 of EO-L in MCF-7 and BEAS-2B cells were 71 and 95 μg/mL, respectively. A combination treatment of EO-L and tamoxifen induced more cell death than the treatment with drug alone at lower doses.
    Matched MeSH terms: Tamoxifen
  13. Khazaei S, Abdul Hamid R, Ramachandran V, Mohd Esa N, Pandurangan AK, Danazadeh F, et al.
    PMID: 29250124 DOI: 10.1155/2017/1468957
    Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF-7 and MDA-MB-231. The extract inhibits the proliferation of the cells in a time- and dose-dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF-7 and S phase arrest in MDA-MB-231 associated with decreased level of Cdk1, in a p53-independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub-G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin-V-positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase-dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC-MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.
    Matched MeSH terms: Tamoxifen
  14. Guthrie N, Gapor A, Chambers AF, Carroll KK
    Asia Pac J Clin Nutr, 1997 Mar;6(1):41-5.
    PMID: 24394652
    Palm oil, unlike many other dietary oils, does not increase the yield of chemically-induced mammary tumors in rats when fed at high levels in the diet. This difference appears to be due to the vitamin E fraction of palm oil, which is rich in tocotrienols, since palm oil stripped of this fraction does increase tumor yields. Experiments in our laboratory have shown that tocotrienols inhibit proliferation and growth of both MDA-MB-435 and MCF-7 cells in culture much more effectively than a-tocopherol. In addition, it was found that combinations of tocotrienols with Tamoxifen, a drug widely used for treatment of breast cancer, inhibit these cells more effectively than either tocotrienols or Tamoxifen alone. The present studies have now shown synergistic effects between tocotrienols and a number of other flavonoids from various plant sources, including citrus fruits, in the inhibition of both MDA-MB-435 and MCF-7 cells (IC50s 0.05-25 and 0.02-5 μg/mL respectively). In the MCF-7 cells, 1:1:1 combinations of tocotrienols, flavonoids and Tamoxifen were even more effective, with the best combination being d-tocotrienol, hesperetin and Tamoxifen (IC50 0.0005 μg/mL). These results suggest that diets containing palm oil may reduce the risk of breast cancer, particularly when eaten with other plant foods containing flavonoids, and may also enhance the effectiveness of Tamoxifen for treatment of breast cancer.
    Matched MeSH terms: Tamoxifen
  15. Shamsabadi FT, Khoddami A, Fard SG, Abdullah R, Othman HH, Mohamed S
    Nutr Cancer, 2013;65(2):255-62.
    PMID: 23441613 DOI: 10.1080/01635581.2013.756528
    The tropical edible red seaweed (Eucheuma cottonii L.) is rich in nutrients and polyphenolic compounds that may suppress cancer through its antioxidant and antiproliferative properties. The study reports on rat mammary tumor suppression and tissue antioxidant status modulation by E. cottonii ethanol extract (ECE). The effect of orally administered ECE (100 mg/kg body-weight) was compared with that of tamoxifen (10 mg/kg body-weight). Rat was induced to develop mammary tumor with subcutaneous injection of LA-7 cells (6 × 10(6) cells/rat). The ECE was more effective than tamoxifen in suppressing tumor growth (27%), improving tissues (plasma, liver, and kidney) malondialdehyde concentrations, superoxide dismutase activity and erythrocyte glutathione concentrations (P < 0.05). Unlike tamoxifen, the ECE displayed little toxicity to the liver and kidneys. The ECE exhibited strong anticancer effect with enzyme modulating properties, suggesting its potential as a suppressing agent for mammary gland tumor.
    Matched MeSH terms: Tamoxifen/pharmacology*
  16. Tiong V, Rozita AM, Taib NA, Yip CH, Ng CH
    World J Surg, 2014 Sep;38(9):2288-96.
    PMID: 24700093 DOI: 10.1007/s00268-014-2542-y
    Breast cancer is increasingly reported in young premenopausal women in Asia. Adjuvant chemotherapy improves survival; however, it has a unique consequence of ovarian failure in premenopausal patients.
    Matched MeSH terms: Tamoxifen/administration & dosage
  17. Samuel MS, Rath N, Masre SF, Boyle ST, Greenhalgh DA, Kochetkova M, et al.
    Genesis, 2016 Dec;54(12):636-646.
    PMID: 27775859 DOI: 10.1002/dvg.22988
    The serine/threonine kinases ROCK1 and ROCK2 are central mediators of actomyosin contractile force generation that act downstream of the RhoA small GTP-binding protein. As a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. Here we describe the generation of a gene-targeted mouse line that enables CRE-inducible expression of a conditionally-active fusion between the ROCK2 kinase domain and the hormone-binding domain of a mutated estrogen receptor (ROCK2:ER). This two-stage system of regulation allows for tissue-selective expression of the ROCK2:ER fusion protein, which then requires administration of estrogen analogues such as tamoxifen or 4-hydroxytamoxifen to elicit kinase activity. This conditional gain-of-function system was validated in multiple tissues by crossing with mice expressing CRE recombinase under the transcriptional control of cytokeratin14 (K14), murine mammary tumor virus (MMTV) or cytochrome P450 Cyp1A1 (Ah) promoters, driving appropriate expression in the epidermis, mammary or intestinal epithelia respectively. Given the interest in ROCK signaling in normal physiology and disease, this mouse line will facilitate research into the consequences of ROCK activation that could be used to complement conditional knockout models. Birth Defects Research (Part A) 106:636-646, 2016. © 2016 Wiley Periodicals, Inc.
    Matched MeSH terms: Tamoxifen/administration & dosage
  18. Bakar NA, Tengku Ibrahim TA, Mohamad Shalan NA, Mohamed S
    J Microsc Ultrastruct, 2016 08 21;5(2):70-81.
    PMID: 30023239 DOI: 10.1016/j.jmau.2016.08.001
    The edible red seaweed Kappaphycus alvarezii or Eucheuma cottonii is commercially cultivated in the pristine tropical seas for carrageenan production. The systemic, cellular, and molecular effects of E. cottonii 50% alcohol extract [seaweed E. cottonii ethanol extract (SECE)] on breast cancer were investigated in a rat model. Mammary tumor was induced by subcutaneously injecting LA7 cells in female rat mammary pads. After 2 weeks of cancer growth, the rats received oral administration of either SECE [150 mg/kg body weight (BW) and 300 mg/kg BW] or tamoxifen. Electron microscopy imaging results confirmed macrophage activity and hematoxylin and eosin staining indicated that tumor histopathological alterations were restored toward normal structures by the seaweed extract. The extract suppressed tumor development and modulated the immune responses. This was evidenced by the microscopic observations, the increased spleen weight, size, spleen CD19 B cells, and blood immunoglobulin G (IgG) levels. The extract also increased the circulating total white blood cells, lymphocytes, segmented neutrophils count, T cells (CD3), T-helper cells (CD4), cytotoxic T cell (CD8), and nuclear factor-kappa beta expressions. The extract enhanced cancer cell death, by upregulating the Birc5, Chk1, and p53 levels and downregulating the tumor growth cellular Mdm2 (transformed mouse 3T3 cell double minute 2) messenger RNA (mRNA) expression. The extract showed no toxicity at 150 mg/kg BW in rats. The lectin-rich SECE showed tumor suppression by enhancing immune responses and upregulating the cancer cell apoptosis mRNA expressions.
    Matched MeSH terms: Tamoxifen
  19. Farghadani R, Seifaddinipour M, Rajarajeswaran J, Abdulla MA, Mohd Hashim NB, Khaing SL, et al.
    PeerJ, 2019;7:e7686.
    PMID: 31608167 DOI: 10.7717/peerj.7686
    Breast cancer is the most frequently diagnosed cancer among women worldwide. Recently, increasing attention has been paid to the anticancer effects of transition metal complexes of indole Schiff bases. β-diiminato ManganeseIII complex has shown promising cell cycle arrest and apoptosis induction against MCF-7 and MDA-MB-231 breast cancer cells. In this study, time- and dose- dependent inhibitory activity were evaluated using MTT assay after 48 h and 72 h exposure time. In addition, median effect analysis was conducted according to Chou-Talalay method to investigate whether MnIII complex has synergistic effect in combination with chemotherapeutic drugs on inhibiting breast cancer cell growth. The molecular mechanisms underlying its potent antiproliferative effect was determined through bioluminescent caspase-3/7, -8 and -9 activity assays and quantitative expression analysis of cell cycle- and apoptosis-related genes. Furthermore, safety evaluation of MnIII complex was assessed through the acute oral toxicity test in in vivo model. The MTT assay results revealed that it potently reduced the viability of MCF-7 (IC50 of 0.63 ± 0.07 µg/mL for 48 h and 0.39 ± 0.08 µg/mL for 72 h) and MDA-MB-231 (1.17 ± 0.06 µg/mL for 48 h, 1.03 ± 0.15 µg/mL for 72 h) cells in dose- and time-dependent manner. Combination treatment also enhanced the cytotoxic effects of doxorubicin but not tamoxifen on inhibiting breast cancer cell growth. The involvement of intrinsic and extrinsic pathway in apoptosis induction was exhibited through the increased activity of caspase-9 and caspase-8, respectively, leading to enhanced downstream executioner caspase-3/7 activity in treated MCF-7 and MDA-MB-231 cells. In addition, gene expression analysis revealed that MnIII complex exerts its antiproliferative effect via up-and down-regulation of p21 and cyclin D1, respectively, along with increased expression of Bax/Bcl-2 ratio, TNF-α, initiator caspase-8 and -10 and effector caspase-3 in MCF-7 and MDA-MB-231 cells. However, the results did not show increased caspase-8 activity in treated MCF-7 cells. Furthermore, in vivo acute oral toxicity test revealed no signs of toxicity and mortality in treated animal models compared to the control group. Collectively, the promising inhibitory effect and molecular and mechanistic evidence of antiproliferative activity of MnIII complex and its safety characterization have demonstrated that it may have therapeutic value in breast cancer treatment worthy of further investigation and development.
    Matched MeSH terms: Tamoxifen
  20. Singh P, Charles S, Madhavan T, Munusamy-Ramanujam G, Saraswathi NT, Arasu MV, et al.
    Eur J Pharmacol, 2021 Jan 15;891:173697.
    PMID: 33144068 DOI: 10.1016/j.ejphar.2020.173697
    We investigated the role of protein arginine methylation (PAM) in estrogen receptor (ER)-positive breast cancer cells through pharmacological intervention. Tamoxifen (TAM) or adenosine dialdehyde (ADOX), independently, triggered cell cycle arrest and down-regulated PAM, as reduced protein arginine methyltransferase1 (PRMT1) mRNA and asymmetric dimethylarginine (ADMA) levels. Synergistic effect of these compounds elicited potent anti-cancer effect. However, reduction in ADMA was not proportionate with the compound-induced down-regulation of PRMT1 mRNA. We hypothesized that the disproportionate effect is due to the influence of the compounds on other methyltransferases, which catalyze the arginine dimethylation reaction and the diversity in the degree of drug-protein interaction among these methyltransferases. In silico analyses revealed that independently, ADOX or TAM, binds with phosphatidylethanolamine-methyltransferase (PEMT) or betaine homocysteine-methyl transferase (BHMT); and that the binding affinity of ADOX with PEMT or BHMT is prominent than TAM. These observations suggest that in breast cancer, synergistic effect of ADOX + TAM elicits impressive protective function by regulating PAM; and plausibly, restoration of normal enzyme activities of methyltransferases catalyzing arginine dimethylation could have clinical benefits.
    Matched MeSH terms: Tamoxifen/metabolism; Tamoxifen/pharmacology*
Filters
Contact Us

Please provide feedback to Administrator ([email protected])

External Links