• Nutrition Research and Practice
• /
• 제7권2호
• /
• pp.89-95
• /
• 2013

Dietary inorganic sulfur is the minor component in our diet, but some studies suggested that inorganic sulfur is maybe effective to treat cancer related illness. Therefore, this study aims to examine the effects of inorganic sulfur on cell proliferation and gene expression in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol/L$) of inorganic sulfur. Inorganic sulfur significantly decreased proliferation after 72 h of incubation (P < 0.05). The protein expression of $ErbB_2$ and its active form, $pErbB_2$, were significantly reduced at inorganic sulfur concentrations of 50 ${\mu}mol/L$ and greater than 25 ${\mu}mol/L$, respectively (P < 0.05). The mRNA expression of $ErbB_2$ was significantly reduced at an inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05). The protein expression of $ErbB_3$ and its active form, $pErbB_3$, and the mRNA expression of $pErbB_3$ were significantly reduced at inorganic sulfur concentrations greater than 25 ${\mu}mol/L$ (P < 0.05). The protein and mRNA expression of Akt were significantly reduced at an inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05), but pAkt was not affected by inorganic sulfur treatment. The protein and mRNA expression of Bax were significantly increased with the addition of inorganic sulfur concentration of 50 ${\mu}mol/L$ (P < 0.05). In conclusion, cell proliferation was suppressed by inorganic sulfur treatment through the ErbB-Akt pathway in MDA-MB-231 cells.

• Molecules and Cells
• /
• 제37권11호
• /
• pp.812-818
• /
• 2014

This study was to investigate the mechanism and role of Kif4A in doxorubicin-induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF-7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP-ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and examined the apoptosis by flow cytometry after treatment with doxorubicin and PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down-regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further demonstrated that overexpression of Kif4A could reduce the level of PAR and significantly increase apoptosis. The effect of doxorubicin on apoptosis was more profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken together, our results suggest that the novel role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP-1.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권7호
• /
• pp.3071-3075
• /
• 2016

Morin, a flavonoid found in figs and other Moraceae species, displays a variety of biological actions, exerting anti-oxidant, anti-inflammatory and anti-carcinogenic effects. Here, we investigated the anti-cancer activity of morin focusing on anti-adhesive influence. We performed experiments with MDA-MB-231 human breast cancer cells. Morin inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. It further inhibited the expression of VCAM-1 on MDA-MB-231 cells as well as HUVECs. Morin also decreased the expression of N-cadherin on MDA-MB-231 cells. In addition, there was apparent anti-metastatic activity in vivo. In conclusion, this study suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM-1, and EMT by targeting N-cadherin, and that it features anti-metastatic activity in vivo. Further investigation of possible anti-metastatic activity of morin against human breast cancer cells is warranted.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.141.1-141.1
• /
• 2003

The inhibitory effect of 13(E)-Labd-13-ene-8$\alpha$ 15-diol(1), isolated from the ethanol extract of Brachyglottis monroi, on the proliferation of human breast cancer MDA-MB231 cells was examined. Compound (1) at concentration as high as 16$\mu$/$m\ell$ has inhibited the proliferation of MDA-MB231 and this cytotoxic effect was increased in a time and dose-dependent manners. (omitted)

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권14호
• /
• pp.5577-5582
• /
• 2014

Objective: To observe the effects of metastasis-associated tumor gene family 2 (MTA2) depletion on human breast cancer cell proliferation and metastasis. Methods: A short-hairpin RNA targeting MTA2 was chemically synthesized and transfected into a lentivirus to construct Lv-shMTA2 for infection into the MDA-MB231 human breast cancer cell line. At 48 hours after infection cells were harvested and mRNA and protein levels of MTA2 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell viability and metastasis were assessed by CCK-8, wound-healing assay and Transwell assay, respectively. In addition, a xenograft model of human breast cancer was constructed to investigate cancerous cell growth and capacity for metastasis. Results: After infection with Lv-shMTA2, mRNA and protein levels of MTA2 was significantly reduced (p<0.05) and MDA-MB231 cell proliferation and metastasis were inhibited (p<0.05). In addition, mean tumor size was smaller than that in control group nude mice (p<0.05) and numbers of metastatic deposits in lung were lower than in control group mice (p<0.05). Depletion of MTA2 affected MMP-2 and apoptosis-related protein expression. Conclusions: For the first time to our knowledge we showed that MTA2 depletion could significantly inhibit human breast cancer cell growth and metastasis, implying that MTA2 might be involved in the progression of breast cancer. The role of MTA2 in breast cancer growth and metastasis might be linked with regulation of matrix metalloproteinase and apoptosis.

• Nutrition Research and Practice
• /
• 제3권4호
• /
• pp.259-264
• /
• 2009

We examined the inhibitory effects of loquat methanol extract on the adhesion, migration, invasion and matrix metalloproteinase (MMP) activities of MDA-MB-231 human breast cancer cell line. Cells were cultured with DMSO or with 10, 25, or 50 ${\mu}g/ml$ of loquat methanol extract. Both leaf and seed extracts significantly inhibited growth of MDA-MB-231 cells in a dose-dependent manner, although leaf extract was more effective. Adhesion and migration were significantly inhibited by loquat extracts in a dose-dependent manner. Loquat extract also inhibited the invasion of breast cancer cells in a dose-dependent manner and leaf extract was more effective than seed extract. MMP-2 and MMP-9 activities were also inhibited by loquat extract. Our results indicate that methanol extracts of loquat inhibit the adhesion, migration and invasion of human breast cancer cells partially through the inhibition of MMP activity and leaf extract has more anti-metastatic effects in cell based assay than seed extract. Clinical application of loquat extract as a potent chemopreventive agent may be helpful in limiting breast cancer invasion and metastasis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권11호
• /
• pp.5709-5714
• /
• 2012

Objective: To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-${\beta}1$ (TGF-${\beta}1$) in MDA-MB-231 cells and potential mechanisms. Methods: Human breast cancer MDA-MB-231 cells were used with the CCK-8 assay to measure the cytotoxicity of curcumin. After treatment with 10 ng/ml TGF-${\beta}1$, with or without curcumin (${\leq}10{\mu}M$), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-${\beta}1$-stimulated MMP-9 and phosphorylation of Smad2, extracellular-regulated kinase (ERK), and p38 mitogen activated protein kinases (p38MAPK) were examined by Western blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Following treatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Western blotting and zymography were employed to examine MMP-9 expression and activity, respectively. Results: Low dose curcumin (${\leq}10{\mu}M$) did not show any obvious toxicity to the cells, while $0{\sim}10{\mu}mol/L$ caused a concentration-dependent reduction in cell invasion provoked by TGF-${\beta}1$. Curcumin also markedly inhibited TGF-${\beta}1$-regulated MMP-9 and activation of Smad2, ERK1/2 and p38 in a dose- and time-dependent manner. Additionally, PD98059, but not SB203580, showed a similar pattern of inhibition of MMP-9 expression. Conclusion: Curcumin inhibited TGF-${\beta}1$-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-${\beta}$/Smad and TGF-${\beta}$/ERK signaling.

• Journal of Microbiology and Biotechnology
• /
• 제24권7호
• /
• pp.914-920
• /
• 2014

Triple-negative breast cancer (TNBC) possesses a higher rate of distant recurrence and a poorer prognosis than other breast cancer subtypes. Interestingly, most of the heat shock protein 90 (Hsp90) client proteins are oncoproteins, and some are closely related to unfavorable factors of TNBC patients. 17-Demethoxy-reblastatin (17-DR), a novel non-benzoquinone-type geldanamycin analog, exhibited potent Hsp90 ATPase inhibition activity. In this study, the anticancer effects of 17-DR on TNBC MDA-MB-231 cells were investigated. These results showed that 17-DR inhibited cell proliferation, induced apoptosis, and suppressed cell invasion and migration in the MDA-MB-231 cells. Down-regulation of the key Hsp90-dependent tumor-driving molecules, such as RIP1 and MMP-9, by 17-DR may be related to these effects. Taken together, our results suggest that 17-DR has potential as a therapeutic agent for the treatment of TNBC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권10호
• /
• pp.6089-6094
• /
• 2013

Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.

• Toxicological Research
• /
• 제21권1호
• /
• pp.77-85
• /
• 2005

Cadmium is an environmental pollutant exposed from contaminated foods or cigarette smoking and known to cause oxidative damage in organs. We investigated the cadmium-induced apoptosis and cell arrest in human breast cancer cells, MCF-7 cells and MDA-MB-231 cells. Obvious apoptotic cell death was shown in CdCl₂ 100 μM treatment for 12 hr, which were determined by DAPI staining and flow cytometric analysis. In cell cycle analysis, MCF-7 cells and MDA-MB-231 cells were arrested in S phase and G2/M phase respectively. These could be explained by the induction of cell cycle inhibitory protein, p21/sup Waf1/Cip1/ and p27/sup Kip1/, expression and reduction of cyclin/Cdk complexes in both cell lines. The decreased expression of cyclin A and Cdk2 in MCF-7 cells and cyclin B1 and Cdc2 in MDA-MB-231 cells were consistent with the flow cytometric observation. p-ERK expression was increased dose-dependent manner in both cell lines. It suggests that ERK MAPK pathway are involved in cadmium-induced cell cycle arrest and apoptosis. Moreover, cotreatment of zinc (100 μM, 12 hr) recovered the cadmium-induced cell arrest in both cells, which shows cadmium-induced oxidative stress mediates apoptosis and cell cycle arrest in human breast cancer cells.