Displaying publications 121 - 140 of 212 in total

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  1. Lua PL, Salihah N, Mazlan N
    Complement Ther Med, 2015 Jun;23(3):396-404.
    PMID: 26051575 DOI: 10.1016/j.ctim.2015.03.009
    OBJECTIVE: To assess the efficacy of inhaled ginger aromatherapy on nausea, vomiting and health-related quality of life (HRQoL) in chemotherapy breast cancer patients.

    DESIGN: Single-blind, controlled, randomized cross-over study. Patients received 5-day aromatherapy treatment using either ginger essential oil or fragrance-matched artificial placebo (ginger fragrance oil) which was instilled in a necklace in an order dictated by the treatment group sequence.

    SETTING: Two oncology clinics in the East Coast of Peninsular Malaysia.

    MAIN OUTCOME MEASURES: VAS nausea score, frequency of vomiting and HRQoL profile (EORTC QLQ-C30 scores).

    RESULTS: Sixty female patients completed the study (age=47.3±9.26 years; Malay=98.3%; on highly emetogenic chemotherapy=86.7%). The VAS nausea score was significantly lower after ginger essential oil inhalation compared to placebo during acute phase (P=0.040) but not sustained for overall treatment effect (treatment effect: F=1.82, P=0.183; time effect: F=43.98, P<0.001; treatment×time effect: F=2.04; P=0.102). Similarly, there was no significant effect of aromatherapy on vomiting [F(1, 58)=0.29, P=0.594]. However, a statistically significant change from baseline for global health status (P<0.001) was detected after ginger essential oil inhalation. A clinically relevant 10 points improvement on role functioning (P=0.002) and appetite loss (P<0.001) were also documented while patients were on ginger essential oil.

    CONCLUSION: At present time, the evidence derived from this study is not sufficiently convincing that inhaled ginger aromatherapy is an effective complementary therapy for CINV. The findings for HRQoL were however encouraging with significant improvement in several domains.

    Matched MeSH terms: Breast Neoplasms/drug therapy
  2. 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/drug therapy
  3. Baharuddin AA, Roosli RAJ, Zakaria ZA, Md Tohid SF
    Pharm Biol, 2018 Dec;56(1):422-432.
    PMID: 30301390 DOI: 10.1080/13880209.2018.1495748
    CONTEXT: Dicranopteris linearis (Burm.f.) Underw. (Gleicheniaceae) has been scientifically proven to exert various pharmacological activities. Nevertheless, its anti-proliferative potential has not been extensively investigated.

    OBJECTIVE: To investigate the anti-proliferative potential of D. linearis leaves and determine possible mechanistic pathways.

    MATERIALS AND METHODS: MTT assay was used to determine the cytotoxic effects of D. linearis methanol (MEDL) and petroleum ether (PEEDL) extracts at concentrations of 100, 50, 25, 12.5, 6.25 and 3.125 µg/mL against a panel of cancer cell lines (breast [MCF-7 and MDA-MB-231], cervical [HeLa], colon [HT-29], hepatocellular [HepG2] and lung [A549]), as compared to negative (untreated) and positive [5-fluorouracil (5-FU)-treated] control groups. Mouse fibroblast cells (3T3) were used as normal cells. The mode of cell death was examined using morphological analysis via acridine orange (AO) and propidium iodide (PI) double staining. Cell cycle arrest was determined using flow cytometer, followed by annexin V-PI apoptosis detection kit.

    RESULTS: MEDL demonstrated the most significant growth inhibition against MDA-MB-231 cells (IC50 22.4 µg/mL). PEEDL showed no cytotoxic effect. Induction of apoptosis by MEDL was evidenced via morphological analysis and acridine orange propidium iodide staining. MEDL could induce S phase cell cycle arrest after 72 h of incubation. Early apoptosis induction in MDA-MB-231 cells was confirmed by annexin V-FITC and PI staining. Significant increase in apoptotic cells were detected after 24 h of treatment with 15.07% cells underwent apoptosis, and the amount escalated to 18.24% with prolonged 48 h incubation.

    CONCLUSIONS: MEDL has potential as a potent cytotoxic agent against MDA-MB-231 adenocarcinoma.

    Matched MeSH terms: Breast Neoplasms/drug therapy
  4. Dawood S, Chiu JW, Huang CS, Nag S, Sookprasert A, Yap YS, et al.
    Curr Med Res Opin, 2020 08;36(8):1363-1373.
    PMID: 32544344 DOI: 10.1080/03007995.2020.1783646
    Breast cancer is the most frequent cancer amongst women worldwide including in Asia where the incidence rate is rapidly increasing. Even with treatment, around 30% of patients with early breast cancer progress to metastatic disease, with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer the most common phenotype. First-line endocrine therapy targeting the estrogen receptor signaling pathway provides a median progression-free survival or time to progression of 6-15 months in HR + HER2- metastatic breast cancer. Recently, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, combined with endocrine therapy, have achieved more than two years median progression-free survival in HR + HER2- metastatic breast cancer. However, the characteristics of the Asian breast cancer population differ from those of Western populations and need to be considered when selecting a suitable treatment. Breast cancer is diagnosed at a younger age in Asian populations and late stage at presentation is generally more common in low-/middle-income countries than high-income countries. Consequently, the proportion of premenopausal women with metastatic breast cancer is higher in Asian compared with Western populations. While CDK4/6 inhibitors have been approved in the USA (FDA) since 2015, experience with them in Asia is more limited. We review the experience with the CDK4/6 inhibitor palbociclib in Asian patients with HR + HER2- metastatic breast cancer and provide guidance on the use of palbociclib in these patients.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  5. Bonde GV, Yadav SK, Chauhan S, Mittal P, Ajmal G, Thokala S, et al.
    Expert Opin Drug Deliv, 2018 05;15(5):495-507.
    PMID: 29521126 DOI: 10.1080/17425247.2018.1449832
    INTRODUCTION: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

    AREAS COVERED: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

    EXPERT OPINION: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.

    Matched MeSH terms: Breast Neoplasms/drug therapy*
  6. Al-Ziftawi NH, Shafie AA, Mohamed Ibrahim MI
    Expert Rev Pharmacoecon Outcomes Res, 2021 Aug;21(4):655-666.
    PMID: 32657174 DOI: 10.1080/14737167.2020.1794826
    BACKGROUND: Pharmacoeconomic evaluation is important for breast-cancer medications due to their high costs. To our knowledge, no systematic literature reviews of pharmacoeconomic studies for breast-cancer medication use are present in developing-countries.

    OBJECTIVES: To systematically review the existing cost-effectiveness evaluations of breast-cancer medication in developing-countries.

    METHODOLOGY: A systematic literature search was performed in PubMed, EMBASE, SCOPUS, and EconLit. Two researchers determined the final articles, extracted data, and evaluated their quality using the Quality of Health-Economic Studies (QHES) tool. The interclass-correlation-coefficient (ICC) was calculated to assess interrater-reliability. Data were summarized descriptively.

    RESULTS: Fourteen pharmacoeconomic studies published from 2009 to 2019 were included. Thirteen used patient-life-years as their effectiveness unit, of which 10 used quality-adjusted life-years. Most of the evaluations focused on trastuzumab as a single agent or on regimens containing trastuzumab (n = 10). The conclusion of cost-effectiveness analysis varied among the studies. All the studies were of high quality (QHES score >75). Interrater reliability between the two reviewers was high (ICC = 0.76).

    CONCLUSION: In many studies included in the review, the use of breast-cancer drugs in developing countries was not cost-effective. Yet, more pharmacoeconomic evaluations for the use of recently approved agents in different disease stages are needed in developing countries.

    Matched MeSH terms: Breast Neoplasms/drug therapy*
  7. Taha H, Looi CY, Arya A, Wong WF, Yap LF, Hasanpourghadi M, et al.
    PLoS One, 2015;10(5):e0126126.
    PMID: 25946039 DOI: 10.1371/journal.pone.0126126
    Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  8. Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M
    Molecules, 2021 Aug 24;26(17).
    PMID: 34500560 DOI: 10.3390/molecules26175119
    α-Mangostin (AMG) is a potent anticancer xanthone that was discovered in mangosteen (Garcinia mangostana Linn.). AMG possesses the highest opportunity for chemopreventive and chemotherapeutic therapy. AMG inhibits every step in the process of carcinogenesis. AMG suppressed multiple breast cancer (BC) cell proliferation and apoptosis by decreasing the creation of cancerous compounds. Accumulating BC abnormalities and their associated molecular signaling pathways promotes novel treatment strategies. Chemotherapy is a commonly used treatment; due to the possibility of unpleasant side effects and multidrug resistance, there has been substantial progress in searching for alternative solutions, including the use of plant-derived natural chemicals. Due to the limitations of conventional cancer therapy, nanotechnology provides hope for effective and efficient cancer diagnosis and treatment. Nanotechnology enables the delivery of nanoparticles and increased solubility of drugs and drug targeting, resulting in increased cytotoxicity and cell death during BC treatment. This review summarizes the progress and development of AMG's cytotoxicity and the mechanism of death BC cells. The combination of natural medicine and nanotechnology into a synergistic capital will provide various benefits. This information will aid in the development of AMG nanoparticle preparations and may open up new avenues for discovering an effective BC treatment.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  9. Seifaddinipour M, Farghadani R, Namvar F, Bin Mohamad J, Muhamad NA
    Molecules, 2020 Apr 13;25(8).
    PMID: 32295069 DOI: 10.3390/molecules25081776
    Pistacia (Pistacia vera) hulls (PV) is a health product that has been determined to contain bioactive phytochemicals which have fundamental importance for biomedical use. In this study, PV ethyl acetate extraction (PV-EA) fractions were evaluated with the use of an MTT assay to find the most cytotoxic fraction, which was found to be F13b1/PV-EA. After that, HPTLC was used for identify the most active compounds. The antioxidant activity was analyzed with DPPH and ABTS tests. Apoptosis induction in MCF-7 cells by F13b1/PV-EA was validated via flow cytometry analysis and a distinctive nuclear staining method. The representation of genes like Caspase 3, Caspase 8, Bax, Bcl-2, CAT and SOD was assessed via a reverse transcription (RT_PCR) method. Inhabitation of Tubo breast cancer cell development was examined in the BALB-neuT mouse with histopathology observations. The most abundant active components available in our extract were gallic acid and the flavonoid quercetin. The F13b1/PV-EA has antiradical activity evidence by its inhibition of ABTS and DPPH free radicals. F13b1/PV-EA displayed against MCF-7 a suppressive effect with an IC50 value of 15.2 ± 1.35 µg/mL. Also, the expression of CAT, SOD, Caspase 3, Caspase 8 and Bax increased and the expression of Bcl-2 decreased. F13b1/PV-EA dose-dependently inhibited tumor development in cancer-induced mice. Thus, this finding introduces F13b1/PV-EA as an effectual apoptosis and antitumor active agent against breast cancer.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  10. Tan ML, Tan HK, Oon CE, Kuroyanagi M, Muhammad TS
    Food Chem Toxicol, 2012 Feb;50(2):431-44.
    PMID: 22101062 DOI: 10.1016/j.fct.2011.11.001
    14-Deoxy-11,12-didehydroandrographolide is one of the principle compounds of the medicinal plant, Andrographis paniculata Nees. This study explored the mechanisms of 14-deoxy-11,12-didehydroandrographolide-induced toxicity and non-apoptotic cell death in T-47D breast carcinoma cells. Gene expression analysis revealed that 14-deoxy-11,12-didehydroandrographolide exerted its cytotoxic effects by regulating genes that inhibit the cell cycle or promote cell cycle arrest. This compound regulated genes that are known to reduce/inhibit cell proliferation, induce growth arrest and suppress cell growth. The growth suppression activities of this compound were demonstrated by a downregulation of several genes normally found to be over-expressed in cancers. Microscopic analysis revealed positive monodansylcadaverine (MDC) staining at 8h, indicating possible autophagosomes. TEM analysis revealed that the treated cells were highly vacuolated, thereby suggesting that 14-deoxy-11,12-didehydroandrographolide may cause autophagic morphology in these cells. This morphology may be correlated with the concurrent expression of genes known to affect lysosomal activity, ion transport, protein degradation and vesicle transport. Interestingly, some apoptotic-like bodies were found, and these bodies contained multiple large vacuoles, suggesting that this compound is capable of eliciting a combination of apoptotic and autophagic-like morphological characteristics.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  11. Chaudhry GE, Jan R, Naveed Zafar M, Mohammad H, Muhammad TST
    Asian Pac J Cancer Prev, 2019 Dec 01;20(12):3555-3562.
    PMID: 31870094 DOI: 10.31557/APJCP.2019.20.12.3555
    OBJECTIVE: Breast cancer is the most frequently diagnosed cancer worldwide. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the extract and fractions of Vitex rotundifolia (leaves) in breast cancer cell line, T-47D.

    METHODS: The cytotoxicity activity was measured using MTS assay. The mode of cell death was analysed by early (phosphatidylserine externalization) and late apoptosis (DNA fragmentation). The caspases 8, 9, 3/7 and apoptotic proteins bax, bcl-2 study were done by western blot and ELISA method.

    RESULTS: The methanol extract was found to inhibit 50% growth of T-47D cells at the concentration of 79.43µg/ml respectively after 72hr. From seven fractions, fraction F1, F2 and F3 produced cytotoxicity effects in T-47D cell line with IC50 (72hr) < 30µg/ml. The results obtained by Annexin V/PI apoptosis detection assay and TUNEL assay suggest that active fractions of  Vitex rotundifolia induced early and late apoptosis (DNA fragmentation) in T-47D cell line. Moreover, western blot analysis and Caspase GloTM luminescent assay demonstrated that fractions F2 and F3 triggered apoptotic cell death via activation of caspases -8, -9 and -3/7 and up-regulation of  Bax and down-regulation of Bcl-2 protein.  Furthermore, chemical profiling confirms the presence of potential metabolites (vitexicarpin) in fractions of Vitex rotundifolia.

    CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in fractions of Vitex rotundifolia as future cancer therapeutic agent for the treatment of breast cancer.
    .

    Matched MeSH terms: Breast Neoplasms/drug therapy*
  12. Dyari HRE, Rawling T, Chen Y, Sudarmana W, Bourget K, Dwyer JM, et al.
    FASEB J, 2017 12;31(12):5246-5257.
    PMID: 28798154 DOI: 10.1096/fj.201700033R
    A saturated analog of the cytochrome P450-mediated ω-3-17,18-epoxide of ω-3-eicosapentaenoic acid (C20E) activated apoptosis in human triple-negative MDA-MB-231 breast cancer cells. This study evaluated the apoptotic mechanism of C20E. Increased cytosolic cytochrome c expression and altered expression of pro- and antiapoptotic B-cell lymphoma-2 proteins indicated activation of the mitochondrial pathway. Caspase-3 activation by C20E was prevented by pharmacological inhibition and silencing of the JNK and p38 MAP kinases (MAPK), upstream MAPK kinases MKK4 and MKK7, and the upstream MAPK kinase kinase apoptosis signal-regulating kinase 1 (ASK1). Silencing of the death receptor TNF receptor 1 (TNFR1), but not Fas, DR4, or DR5, and the adapters TRADD and TNF receptor-associated factor 2, but not Fas-associated death domain, prevented C20E-mediated apoptosis. B-cell lymphoma-2 homology 3-interacting domain death agonist (Bid) cleavage by JNK/p38 MAPK linked the extrinsic and mitochondrial pathways of apoptosis. In further studies, an antibody against the extracellular domain of TNFR1 prevented apoptosis by TNF-α but not C20E. These findings suggest that C20E acts intracellularly at TNFR1 to activate ASK1-MKK4/7-JNK/p38 MAPK signaling and to promote Bid-dependent mitochondrial disruption and apoptosis. Inin vivostudies, tumors isolated from C20E-treated nu/nu mice carrying MDA-MB-231 xenografts showed increased TUNEL staining and decreased Ki67 staining, reflecting increased apoptosis and decreased proliferation, respectively. ω-3-Epoxy fatty acids like C20E could be incorporated into treatments for triple-negative breast cancers.-Dyari, H. R. E., Rawling, T., Chen, Y., Sudarmana, W., Bourget, K., Dwyer, J. M., Allison, S. E., Murray, M. A novel synthetic analogue of ω-3 17,18-epoxyeicosatetraenoic acid activates TNF receptor-1/ASK1/JNK signaling to promote apoptosis in human breast cancer cells.
    Matched MeSH terms: Breast Neoplasms/drug therapy
  13. Biswal BM, Sulaiman SA, Ismail HC, Zakaria H, Musa KI
    Integr Cancer Ther, 2013 Jul;12(4):312-22.
    PMID: 23142798 DOI: 10.1177/1534735412464551
    Hypothesis. Withania somnifera is an herb with antioxidant, anti-inflammatory, anticancer, antistress, and adaptogenic properties. Previous studies have shown its antistress effects in animals. Traditional Indian medicine has used it for centuries to alleviate fatigue and improve general well-being.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  14. Paydar M, Kamalidehghan B, Wong YL, Wong WF, Looi CY, Mustafa MR
    Drug Des Devel Ther, 2014;8:719-33.
    PMID: 24944509 DOI: 10.2147/DDDT.S58178
    To date, plants have been the major source of anticancer drugs. Boldine is a natural alkaloid commonly found in the leaves and bark of Peumus boldus. In this study, we found that boldine potently inhibited the viability of the human invasive breast cancer cell lines, MDA-MB-231 (48-hour IC₅₀ 46.5±3.1 μg/mL) and MDA-MB-468 (48-hour IC₅₀ 50.8±2.7 μg/mL). Boldine had a cytotoxic effect and induced apoptosis in breast cancer cells as indicated by a higher amount of lactate dehydrogenase released, membrane permeability, and DNA fragmentation. In addition, we demonstrated that boldine induced cell cycle arrest at G2/M phase. The anticancer mechanism is associated with disruption of the mitochondrial membrane potential and release of cytochrome c in MDA-MB-231. Boldine selectively induced activation of caspase-9 and caspase-3/7, but not caspase-8. We also found that boldine could inhibit nuclear factor kappa B activation, a key molecule in tumor progression and metastasis. In addition, protein array and Western blotting analysis showed that treatment with boldine resulted in downregulation of Bcl-2 and heat shock protein 70 and upregulation of Bax in the MDA-MB-231 cell line. An acute toxicity study in rats revealed that boldine at a dose of 100 mg/kg body weight was well tolerated. Moreover, intraperitoneal injection of boldine (50 or 100 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that boldine is a potentially useful agent for the treatment of breast cancer.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  15. Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, et al.
    PLoS One, 2013;8(2):e56643.
    PMID: 23437193 DOI: 10.1371/journal.pone.0056643
    Centratherum anthelminticum (L.) seeds (CA) is a well known medicinal herb in Indian sub-continent. We recently reported anti-oxidant property of chloroform fraction of Centratherum anthelminticum (L.) seeds (CACF) by inhibiting tumor necrosis factor-α (TNF-α)-induced growth of human breast cancer cells. However, the active compounds in CACF have not been investigated previously.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  16. Hasanpourghadi M, Majid NA, Mustafa MR
    Biochem Pharmacol, 2018 06;152:174-186.
    PMID: 29608909 DOI: 10.1016/j.bcp.2018.03.030
    We recently reported that methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) is a microtubule targeting agent (MTA) with multiple mechanisms of action including apoptosis in two human breast cancer cell-lines MCF-7 and MDA-MB-231. In the present study, investigation of early molecular events following MBIC treatment demonstrated the induction of autophagy. This early (<24 h) response to MBIC was characterized by accumulation of autophagy markers; LC3-II, Beclin1, autophagic proteins (ATGs) and collection of autophagosomes but with different variations in the two cell-lines. MBIC-induced autophagy was associated with generation of reactive oxygen species (ROS). In parallel, an increased activation of SAPK/JNK pathway was detected, as an intersection of ROS production and induction of autophagy. The cytotoxic effect of MBIC was enhanced by inhibition of autophagy through blockage of SAPK/JNK signaling, suggesting that MBIC-induced autophagy, is a possible cellular self-defense mechanism against toxicity of this agent in both breast cancer cell-lines. The present findings suggest that inhibition of autophagy eliminates the cytoprotective activity of MDA-MB-231 and MCF-7 cells, and sensitizes both the aggressive and non-aggressive human breast cancer cell-lines to the cytotoxic effects of MBIC.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  17. Hasanpourghadi M, Pandurangan AK, Karthikeyan C, Trivedi P, Mustafa MR
    Oncotarget, 2017 Apr 25;8(17):28840-28853.
    PMID: 28392503 DOI: 10.18632/oncotarget.16263
    Microtubule Targeting Agents (MTAs) induce cell death through mitotic arrest, preferentially affecting rapidly dividing cancer cells over slowly proliferating normal cells. Previously, we showed that Methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) acts as a potential MTA. In this study, we demonstrated that MBIC exhibits greater toxicity towards non-aggressive breast cancer cell-line, MCF-7 (IC50 = 0.73 ± 0.0 μM) compared to normal fibroblast cell-line, L-cells (IC50 = 59.6 ± 2.5 μM). The IC50 of MBIC against the aggressive breast cancer cell-line, MDA-MB-231 was 20.4 ± 0.2 μM. We hypothesized that the relatively high resistance of MDA-MB-231 cells to MBIC is associated with p53 mutation. We investigated p53 and three of its downstream proteins: survivin, cyclin dependent kinase (Cdk1) and cyclin B1. Following treatment with MBIC, survivin co-immunoprecipitated with caspases with higher affinity in MDA-MB-231 compared to MCF-7 cells. Furthermore, silencing survivin caused a 4.5-fold increase in sensitivity of MDA-MB-231 cells to MBIC (IC50 = 4.4 ± 0.3). In addition, 4 weeks of MBIC administration in MDA-MB-231 cells inoculated BALB/c nude mice resulted in 79.7% reduction of tumor volume compared to the untreated group with no severe sign of toxicity. Our results demonstrated MBIC has multiple anti-tumor actions and could be a potential drug in breast cancer therapy.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  18. Hasanpourghadi M, Pandurangan AK, Mustafa MR
    Pharmacol Res, 2018 02;128:376-388.
    PMID: 28923544 DOI: 10.1016/j.phrs.2017.09.009
    Carcinogenesis, a multi-step phenomenon, characterized by alterations at genetic level and affecting the main intracellular pathways controlling cell growth and development. There are growing number of evidences linking oncogenes to the induction of malignancies, especially breast cancer. Modulations of oncogenes lead to gain-of-function signals in the cells and contribute to the tumorigenic phenotype. These signals yield a large number of proteins that cause cell growth and inhibit apoptosis. Transcription factors such as STAT, p53, NF-κB, c-JUN and FOXM1, are proteins that are conserved among species, accumulate in the nucleus, bind to DNA and regulate the specific genes targets. Oncogenic transcription factors resulting from the mutation or overexpression following aberrant gene expression relay the signals in the nucleus and disrupt the transcription pattern. Activation of oncogenic transcription factors is associated with control of cell cycle, apoptosis, migration and cell differentiation. Among different cancer types, breast cancer is one of top ten cancers worldwide. There are different subtypes of breast cancer cell-lines such as non-aggressive MCF-7 and aggressive and metastatic MDA-MB-231 cells, which are identified with distinct molecular profile and different levels of oncogenic transcription factor. For instance, MDA-MB-231 carries mutated and overexpressed p53 with its abnormal, uncontrolled downstream signalling pathway that account for resistance to several anticancer drugs compared to MCF-7 cells with wild-type p53. Appropriate enough, inhibition of oncogenic transcription factors has become a potential target in discovery and development of anti-tumour drugs against breast cancer. Plants produce diverse amount of organic metabolites. Universally, these metabolites with biological activities are known as "natural products". The chemical structure and function of natural products have been studied since 1850s. Investigating these properties leaded to recognition of their molecular effects as anticancer drugs. Numerous natural products extracted from plants, fruits, mushrooms and mycelia, show potential inhibitory effects against several oncogenic transcription factors in breast cancer. Natural compounds that target oncogenic transcription factors have increased the number of candidate therapeutic agents. This review summarizes the current findings of natural products in targeting specific oncogenic transcription factors in breast cancer.
    Matched MeSH terms: Breast Neoplasms/drug therapy
  19. Zulkipli AF, Islam T, Mohd Taib NA, Dahlui M, Bhoo-Pathy N, Al-Sadat N, et al.
    Integr Cancer Ther, 2018 06;17(2):312-321.
    PMID: 29218996 DOI: 10.1177/1534735417745248
    BACKGROUND: The use of complementary and alternative medicine (CAM) has increased and little is known on CAM use during the initial period. Therefore, the aim was to determine prevalence of CAM use among newly diagnosed breast cancer patients prior to seeking conventional treatment.

    METHODS: This is a cross-sectional study involved interviewing newly diagnosed breast cancer patients in the University Malaya Medical Centre (UMMC) using a structured questionnaire. Eligible respondents were interviewedduring a routine clinical visit.

    RESULTS: A total of 400 patients were interviewed, of whom 139 (34.8%) were CAM users. Dietary supplementation (n = 107, 77.0%) was the most frequently used type of CAM, followed by spiritual healing (n = 40, 28.8%) and traditional Chinese medicine (n = 32, 23.0%). Malay ethnic group (n = 61, 43.9%) was the largest group of CAM users, followed by Chinese (n = 57, 41.0%) and Indian (n = 20, 14.4%). Majority of these CAM users (n = 87, 73.1%) did not disclose the use of CAM to their doctors. Most of them used remedies based on the recommendation of family and friends. Malay ethnicity and patients with 3 or more comorbidities were more likely to use CAM.

    CONCLUSION: There is substantial use of CAM among breast cancer patients in UMMC prior to seeking hospital treatment, and the most popular CAM modality is dietary supplements. Since, the majority of CAM users do not disclose the use of CAM to their physicians, therefore health care providers should ensure that those patients who are likely to use CAM are appropriately counseled and advised.

    Matched MeSH terms: Breast Neoplasms/drug therapy*
  20. In LL, Azmi MN, Ibrahim H, Awang K, Nagoor NH
    Anticancer Drugs, 2011 Jun;22(5):424-34.
    PMID: 21346553 DOI: 10.1097/CAD.0b013e328343cbe6
    In this study, the apoptotic mechanism and combinatorial chemotherapeutic effects of the cytotoxic phenylpropanoid compound 1'S-1'-acetoxyeugenol acetate (AEA), extracted from rhizomes of the Malaysian ethnomedicinal plant Alpinia conchigera Griff. (Zingiberaceae), on MCF-7 human breast cancer cells were investigated for the first time. Data from cytotoxic and apoptotic assays such as live and dead and poly-(ADP-ribose) polymerase cleavage assays indicated that AEA was able to induce apoptosis in MCF-7 cells, but not in normal human mammary epithelial cells. A microarray global gene expression analysis of MCF-7 cells, treated with AEA, suggested that the induction of tumor cell death through apoptosis was modulated through dysregulation of the nuclear factor-kappaB (NF-κB) pathway, as shown by the reduced expression of various κB-regulated gene targets. Consequent to this, western blot analysis of proteins corresponding to the NF-κB pathway indicated that AEA inhibited phosphorylation levels of the inhibitor of κB-kinase complex, resulting in the elimination of apoptotic resistance originating from NF-κB activation. This AEA-based apoptotic modulation was elucidated for the first time in this study, and gave rise to the proposal of an NF-κB model termed the 'Switching/Alternating Model.' In addition to this, AEA was also found to synergistically enhance the proapoptotic effects of paclitaxel, when used in combination with MCF-7 cells, presumably by a chemosensitizing role. Therefore, it was concluded that AEA isolated from the Malaysian tropical ginger (A. conchigera) served as a very promising candidate for further in-vivo development in animal models and in subsequent clinical trials involving patients with breast-related malignancies.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
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