• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8431-8438
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• 2016

Doxorubicin (DOX) was introduced as an effective chemotherapeutic for a wide range of cancers but with some severe side effects especially on myocardia. 2-Deoxy-D-glucose (2DG) enhances the damage caused by chemotherapeutics and ionizing radiation (IR) selectively in cancer cells. We have studied the effects of $1{\mu}M$ DOX and $500{\mu}M$ 2DG on radiation induced cell death, apoptosis and also on the expression levels of p53 and PTEN genes in T47D and SKBR3 breast cancer cells irradiated with 100, 150 and 200 cGy x-rays. DOX and 2DG treatments resulted in altered radiation-induced expression levels of p53 and PTEN genes in T47D as well as SKBR3 cells. In addition, the combination along with IR decreased the viability of both cell lines. The radiobiological parameter (D0) of T47D cells treated with 2DG/DOX and IR was 140 cGy compared to 160 cGy obtained with IR alone. The same parameters for SKBR3 cell lines were calculated as 120 and 140 cGy, respectively. The sensitivity enhancement ratios (SERs) for the combined chemo-radiotherapy on T47D and SKBR3 cell lines were 1.14 and 1.16, respectively. According to the obtained results, the combination treatment may use as an effective targeted treatment of breast cancer either by reducing the single modality treatment side effects.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3835-3838
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• 2016

Background: Breast cancer is one of the most frequent cancer types within female populations. Silibinin is a chemotherapeutic agent ative against cancer. Niosomes are biodegradable, biocompatible, safe and effective carriers for drug delivery. Objective:To prepare nanoniosomal silibinin and evaluate its cytotoxicity inthe T-47D breast cancer cell line. Materials and Methods: Niosomes were prepared by reverse phase evaporation of a mixture of span 20, silibinin, PEG-2000 and cholesterol in chloroform and methanol solvent (1:2 v/v). The solvent phase was evaporated using a rotary evaporator and the remaining gel phase was hydrated in phosphate buffer saline. Mean size, size distribution and zeta potential of niosomes were measured with a Zetasizer instrument and then nanoparticles underwent scanning electron microscopy. The drug releasing pattern was evaluated by dialysis and the cytotoxicity of nanoniosomes in T-47D cells was assessed by MTT assay. Results: Particle size, size variation and zeta potential of the niosomal nanoparticles were measured as $178.4{\pm}5.4nm$, $0.38{\pm}0.09$ and $-15.3{\pm}1.3mV$, respectively. The amount of encapsulated drug and the level of drug loading were determined $98.6{\pm}2.7%$ and $22.3{\pm}1.8%$, respectively; released drug was estimated about $18.6{\pm}2.5%$ after 37 hours. The cytotoxic effects of nanoniosome were significantly increased when compared with the free drug. Conclusions: This study finding suggests that silibinin nanoniosomes could serve as a new drug formulation for breast cancer therapy.

• Archives of Pharmacal Research
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• 제20권6호
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• pp.566-571
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• 1997

To gain further insight into how estrogens modulate cell function, the effects of estrogen on cell proliferation were studied inhuman breast cancer cells. We examined the effects of estrogen on the proliferation of three human breast cancer cell lines that differed in their estrogen receptor contents. Ten nM estradiol markedly stimulated the proliferation of MCF-7 human breast cancer cells that contained high levels of estrogen receptor $1.15{\pm}0.03 pmole/mg protein)$(over that of control. In T47D cells that contained low levels of estrogen receptor $0.23{\pm}0.05 pmole/mg protein)$, Ten nM estrogen slightly stimulated the proliferation over that of control. MDA-MB-231 cells, that contained no detectable levels of estrogen receptors, had their growth unaffected by estrogen. These results showed their sensitivity to growth stimulation by estrogen correlated well with their estrogen receptor content. Also we examined the effect of estrogen on cellular progesterone receptor level as well as plasminogen activator activity in MCF-7 cells. Ten nM estradiol showed maximal stimulation of progesterone receptor level as well as plasminogen activator activity in MCF-7 cells. It is not clear whether these stimulations of progesterone receptor and plasminogen activator activity by estrogen are related to the estrogen stimulation of cell proliferation of MCF-7 cells. Studies with estrogen in human breast cancer cells in culture indicate that sensitivity to growth stimulation by estrogen correlates well with estrogen receptor contents.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.615-618
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• 2016

Ethyl acetate extracts obtained from culture of endophytic fungi Aspergillus sp isolated from Piper crocatum Ruiz & Pav, have been shown to possess cytotoxic activity against T47D breast cancer cells. Investigations were here conducted to determine bioactive compounds responsible for the activity. Bioassay guided fractionation was employed to obtain active compounds. Structure elucidation was performed based on analysis of LC-MS, $^1H$-NMR, $^{13}C$-NMR, COSY, DEPT, HMQC, HMBC data. Cytotoxity assays were conducted in 96 well plates against T47D and Vero cell lines. Bioassay guided isolation and chemical investigation led to the isolation of pyrophen, a 4-methoxy-6-(1'-acetamido-2'-phenylethyl)-2H-pyran-2-one. Further analysis of its activity against T47D and Vero cells showed an ability to inhibit the growth of T47D cells with IC50 values of $9.2{\mu}g/mL$ but less cytotoxicity to Vero cells with an $IC_{50}$ of $109{\mu}g/mL$. This compound at a concentration of 400 ng/mL induced S-phase arrest in T47D cells.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2453-2457
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• 2016

Background: Dysregulation of HSP90 gene expression is known to take place in breast cancer. Here we used D,L-lactic-co-glycolic acid-polyethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG to inhibit the expression of HSP90 gene in the T47D breast cancer cell line. The purpose was to determine whether nanoencapsulating 17DMAG improves the anti-cancer effects as compared to free 17DMAG. Materials and Methods: The T47D breast cancer cell line was grown in RPMI 1640 supplemented with 10% FBS. Encapsulation of 17DMAG was conducted through a double emulsion method and properties of copolymers were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity was by MTT assay. After treatment of T47D cells with a given amount of drug, RNA was extracted and cDNA was synthesized. In order to assess HSP90 gene expression, real-time PCR was performed. Results: Taking into account drug load, IC50 was significant decreased in nanocapsulated 17DMAG in comparison with free 17DMAG. This finding was associated with decrease of HSP90 gene expression. Conclusions: PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of HSP90 expression, at the saesm time exerting more potent cytotoxic effects. Therefore, PLGA-PEG could be a superior carrier for this type of hydrophobic agent.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3449-3453
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• 2013

Background: Telomerase has been considered as an attractive molecular target for breast cancer therapy. The main objective of this work is to assess the inhibitory effects of silibinin and curcumin, two herbal substances, on telomerase gene expression in breast cancer cells. Materials and Methods: For determination of cell viability tetrazolium-based assays were conducted after 24, 48, and 72 h exposure times and expression of human telomerase reverse transcriptase gene was measured with real-time PCR. Results: Each compound exerted cytotoxic effects on T47D cells and inhibited telomerase gene expression, both in a time-and dose-dependent manner. The mixture of curcumin and silibinin showed relatively more inhibitory effect on growth of T47D cells and hTERT gene expression as compared with either agent alone. Conclusions: These findings suggest that cell viability along with hTERT gene expression in breast cancer cells could be reduced by curcumin and silibinin.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6595-6599
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• 2013

Leptin and its receptor are involved in breast carcinogenesis as mitogenic factors. Therefore, they could be considered as targets for breast cancer therapy. Expression of the leptin receptor gene could be modulated by leptin secretion. Silibinin and curcumin are herbal compounds with anti-cancer activity against breast cancer. The aim of this study was to assess their potential to inhibit of expression of the leptin gene and its receptor and leptin secretion. Cytotoxic effects of the two agents on combination on T47D breast cancer cells was investigated by MTT assay test after 24h treatment. With different concentrations the levels of leptin, leptin receptor genes expression were measured by reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. The silibinin and curcumin combination inhibited growth of T47D cells in a dose dependent manner. There were also significant difference between control and treated cells in leptin expression and the quantity of secreted leptin with a relative decrease in leptin receptor expression. In conclusion, these herbal compounds inhibit the expression and secretion of leptin and it could probably be used as drug candidates for breast cancer therapy through leptin targeting in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1967-1971
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• 2016

Background: In tumor cells, aberrant differentiation programs have been described. Several neuronal proteins have been found associated with morphological neuronal-glial changes in breast cancer (BCa). These neuronal proteins have been related to mechanisms that are involved in carcinogenesis; however, this regulation is not well understood. Microtubule-associated protein-tau (MAP-Tau) has been describing in BCa but not its variants. This finding could partly explain the neuronal-glial morphology of BCa cells. Our aim was to determine mRNA expression of MAP-tau variants 2, 4 and 6 in breast cancer cell lines. Materials and Methods: Cultured cell lines MCF-10A, MDA-MB-231, SKBR3 and T47D were observed under phase-contrast microscopy for neural morphology and analyzed for gene expression of MAP-Tau transcript variants 2, 4 and 6 by real-time PCR. Results: Regarding morphology like neural/glial cells, T47D line shown more cells with these features than MDA-MB-231 and SKBR. In another hand, we found much greater mRNA expression of MAP-Tau transcript variants 2, and to a lesser extent 4 and 6, in T47D cells than the other lines. In conclusion, regulation of MAP-Tau could bring about changes in cytoskeleton, cell morphology and motility; these findings cast further light on neuronal transdifferentiation in BCa.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2277-2284
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• 2016

Ribosome-inactivating protein (RIP) from Mirabilis jalapa L. leaves has cytotoxic effects on breast cancer cell lines but is less toxic towards normal cells. However, it can easily be degraded after administration so it needs to be formulated into nanoparticles to increase its resistance to enzymatic degradation. The objectives of this study were to develop a protein extract of M. jalapa L. leaves (RIP-MJ) incorporated into nanoparticles conjugated with Anti-EpCAM antibodies, and to determine its cytotoxicity and selectivity in the T47D breast cancer cell line. RIP-MJ was extracted from red-flowered M. jalapa L. leaves. Nanoparticles were formulated based on polyelectrolyte complexation using low viscosity chitosan and alginate, then chemically conjugated with anti-EpCAM antibody using EDAC based on carbodiimide reaction. RIP-MJ nanoparticles were characterised for the particle size, polydispersity index, zeta potential, particle morphology, and entrapment efficiency. The cytotoxicity of RIP-MJ nanoparticles against T47D and Vero cells was then determined with MTT assay. The optimal formula of RIP-MJ nanoparticles was obtained at the concentration of RIP-MJ, low viscosity chitosan and alginate respectively 0.05%, 1%, and 0.4% (m/v). RIP-MJ nanoparticles are hexagonal with high entrapment efficiency of 98.6%, average size of 130.7 nm, polydispersity index of 0.380 and zeta potential +26.33 mV. The $IC_{50}$ values of both anti-EpCAM-conjugated and non-conjugated RIP-MJ nanoparticles for T47D cells (13.3 and $14.9{\mu}g/mL$) were lower than for Vero cells (27.8 and $33.6{\mu}g/mL$). The $IC_{50}$ values of conjugated and non-conjugated RIP-MJ for both cells were much lower than $IC_{50}$ values of non-formulated RIP-MJ (>$500{\mu}g/mL$).

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.23-23
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• 2003

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon (AhR) ligands suppress 17${\beta}$-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent degradation of endogenous estrogen receptor ${\alpha}$ (ER${\alpha}$).(omitted)