• Title, Summary, Keyword: breast cancer cell proliferation

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PKCδ-dependent Activation of the Ubiquitin Proteasome System is Responsible for High Glucose-induced Human Breast Cancer MCF-7 Cell Proliferation, Migration and Invasion

  • Zhu, Shan;Yao, Feng;Li, Wen-Huan;Wan, Jin-Nan;Zhang, Yi-Min;Tang, Zhao;Khan, Shahzad;Wang, Chang-Hua;Sun, Sheng-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5687-5692
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    • 2013
  • Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta ($PKC{\delta}$)-phosphorylation. Administration of the specific $PKC{\delta}$ inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, $PKC{\delta}$ inhibition by both rottlerin and $PKC{\delta}$ shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that $PKC{\delta}$-dependent ubiquitin proteasome system activation plays an important role in high glucose-induced breast cancer cell growth and metastasis.

Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells

  • Park, Soo-Jin;Lee, Kyoung-Pil;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • v.22 no.2
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    • pp.129-135
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    • 2014
  • Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) via type 1 lysophosphatidic acid (LPA) receptor ($LPA_1$) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like $LPA_1/CD97-G_{i/o}$ proteins-phospholipase $C-IP_3-Ca^{2+}$ increase in these cells. In the present study, we further investigated actions of LPE not only in the $[Ca^{2+}]_i$ increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of $LPA_1$, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced $Ca^{2+}$ response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced $Ca^{2+}$ response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting $LPA_1$ involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced $Ca^{2+}$ response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not $LPA_1$) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized $LPA_1$, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.

Garcinol, an Acetyltransferase Inhibitor, Suppresses Proliferation of Breast Cancer Cell Line MCF-7 Promoted by 17β-Estradiol

  • Ye, Xia;Yuan, Lei;Zhang, Li;Zhao, Jing;Zhang, Chun-Mei;Deng, Hua-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.5001-5007
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    • 2014
  • The acetyltransferase inhibitor garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Anti-cancer activity has been suggested but there is no report on its action via inhibiting acetylation against cell proliferation, cell cycle progression, and apoptosis-inhibtion induced by estradiol ($E_2$) in human breast cancer MCF-7 cells. The main purposes of this study were to investigate the effects of the acetyltransferase inhibitor garcinol on cell proliferation, cell cycle progression and apoptosis inhibition in human breast cancer MCF-7 cells treated with estrogen, and to explore the significance of changes in acetylation levels in this process. We used a variety of techniques such as CCK-8 analysis of cell proliferation, FCM analysis of cell cycling and apoptosis, immunofluorescence analysis of NF-${\kappa}B$/p65 localization, and RT-PCR and Western blotting analysis of ac-H3, ac-H4, ac-p65, cyclin D1, Bcl-2 and Bcl-xl. We found that on treatment with garcinol in MCF-7 cells, $E_2$-induced proliferation was inhibited, cell cycle progression was arrested at G0/G1 phase, and the cell apoptosis rate was increased. Expression of ac-H3, ac-H4 and NF-${\kappa}B$/ac-p65 proteins in $E_2$-treated MCF-7 cells was increased, this being inhibited by garcinol but not ac-H4.The nuclear translocation of NF-${\kappa}B$/p65 in $E_2$-treated MCF-7 cells was also inhibited, along with cyclin D1, Bcl-2 and Bcl-xl in mRNA and protein expression levels. These results suggest that the effect of $E_2$ on promoting proliferation and inhibiting apoptosis is linked to hyperacetylation levels of histones and nonhistone NF-${\kappa}B$/p65 in MCF-7 cells. The acetyltransferase inhibitor garcinol plays an inhibitive role in MCF-7 cell proliferation promoted by $E_2$. Mechanisms are probably associated with decreasing ac-p65 protein expression level in the NF-${\kappa}B$ pathway, thus down-regulating the expression of cyclin D1, Bcl-2 and Bcl-xl.

Effects of $\alpha$-lipoic acid on cell proliferation and apoptosis in MDA-MB-231 human breast cells

  • Na, Mi-Hee;Seo, Eun-Young;Kim, Woo-Kyoung
    • Nutrition Research and Practice
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    • v.3 no.4
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    • pp.265-271
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    • 2009
  • The role that antioxidants play in the process of carcinogenesis has recently gained considerable attention. $\alpha$-Lipoic acid, a naturally occurring disulfide molecule, is a powerful antioxidant that reportedly exerts beneficial effects in patients with advanced cancer by reducing the level of reactive oxygen species and increasing glutathione peroxidase activity. In this study, we examined changes in the protein and mRNA expression associated with cell proliferation and apoptosis in MDA-MB-231 breast cancer cultured in the presence of various concentrations (0, 250, 500, and 1000 ${\mu}mol/L$) of $\alpha$-lipoic acid. The results revealed that $\alpha$-lipoic acid inhibited the growth of breast cancer cells in a dose-independent manner (P < 0.05). Additionally, $ErbB_2$ and $ErbB_3$ protein and mRNA expressions were significantly decreased in a dose-dependent manner in response to $\alpha$-lipoic acid (P < 0.05). Furthermore, the protein expression of phosphorylated Akt (p-Akt) levels and total Akt, and the mRNA expression of Akt were decreased dose-dependently in cells that were treated with $\alpha$-lipoic acid (P < 0.05). Bcl-2 protein and mRNA expressions were also decreased in cells that were treated with $\alpha$-lipoic acid (P < 0.05). However, Bax protein and mRNA expressions were increased in cells treated with $\alpha$-lipoic acid (P < 0.05). Finally, caspase-3 activity was significantly increased in a dose-dependent manner in cells treated with $\alpha$-lipoic acid (P < 0.05). In conclusion, we demonstrated that $\alpha$-lipoic acid inhibits cell proliferation and induces apoptosis in MDA-MB-231 breast cancer cell lines.

Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells

  • Choi, Eun-Jeong;Ahn, Woong-Shick
    • Nutrition Research and Practice
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    • v.2 no.4
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    • pp.322-325
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    • 2008
  • The aim of present study was to investigate the effects of kaempferol on cellular proliferation and cell cycle arrest and explore the mechanism for these effects in human breast carcinoma MDA-MB-453 cells. Cells were treated with kaempferol at various concentrations (ranging from 1 to $200\;{\mu}M$) for 24 and 48 hrs. Kaempferol significantly inhibited cancer cell growth in cells exposed to 50 and $10\;{\mu}M$ of kaempferol and incubated for 24 and 48 hrs, respectively. Exposure to kaempferol resulted in cell cycle arrest at the G2/M phase. Of the G2/M-phase related proteins, kaempferol down-regulated CDK1 and cyclin A and B in cells exposed to kaempferol. In addition, small DNA fragments at the sub-G0 phase were increased by up to 23.12 and 31.90% at 10 and $50\;{\mu}M$ incubated for 24 and 48 hrs, respectively. The kaempferol-induced apoptosis was associated with the up-regulation of p53. In addition, the phosphorylation of p53 at the Ser-15 residue was observed with kaempferol. Kaempferol inhibits cell proliferation by disrupting the cell cycle, which is strongly associated with the induction of arrest at G2/M phase and may induce apoptosis via p53 phosphorylation in human breast carcinoma MDA-MB-453 cells.

Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells

  • Liu, Qiuming;Cao, Yali;Zhou, Ping;Gui, Shimin;Wu, Xiaobo;Xia, Yong;Tu, Jianhong
    • Biomolecules & Therapeutics
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    • v.26 no.3
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    • pp.328-334
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    • 2018
  • Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anticancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dose-dependent inhibition of cell growth with an $IC_{50}$ of $15{\mu}M$ and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dose-dependent (i) induction of $p21^{WAF1/Cip1}$ and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.

Curdione Inhibits Proliferation of MCF-7 Cells by Inducing Apoptosis

  • Li, Juan;Bian, Wei-He;Wan, Juan;Zhou, Jing;Lin, Yan;Wang, Ji-Rong;Wang, Zhao-Xia;Shen, Qun;Wang, Ke-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9997-10001
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    • 2014
  • Background: Curdione, one of the major components of Curcuma zedoaria, has been reported to possess various biological activities. It thus might be a candidate anti-flammatory and cancer chemopreventive agent. However, the precise molecular mechanisms of action of curdione on cancer cells are still unclear. In this study, we investigated the effect of curdione on breast cancer. Materials and Methods: Xenograft nude mice were used to detect the effect of curdione on breast cancer in vivo; we also tested the effect of curdione on breast cancer in vitro by MTT, Flow cytometry, JC-I assay, and western blot. Results: Firstly, we found that curdione significantly suppressed tumor growth in a xenograft nude mouse breast tumor model in a dose-dependent manner. In addition, curdione treatment inhibited cell proliferation and induced cell apoptosis. Moreover, after curdione treatment, increase of impaired mitochondrial membrane potential occurred in a concentration dependent manner. Furthermore, the expression of apoptosis-related proteins including cleaved caspase-3, caspase-9 and Bax was increased in curdione treatment groups, while the expression of the anti-apoptotic Bcl-2 was decreased. Inhibitors of caspase-3 were used to confirm that curdione induced apoptosis. Conclusions: Overall, our observations first suggested that curdione inhibited the proliferation of breast cancer cells by inducing apoptosis. These results might provide some molecular basis for the anti-cancer activity of curdione.

Inhibitory Effects of Harmine on Migration and Invasion of Human Breast Cancer Cells by Regulating Notch Signaling (Harmine의 Notch 신호전달 조절에 의한 유방암세포주 이동 및 침윤 억제 효과)

  • Yun, Jieun
    • Korean Journal of Pharmacognosy
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    • v.49 no.4
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    • pp.285-290
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    • 2018
  • Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala has been reported as a promising drug candidate for cancer therapy. However, the effect of harmine on breast cancer remains still unclear. In this study, the effect of harmine on the cell proliferation, migration, and invasion of breast cancer MDA-MB231 cells and the underlying mechanism were investigated. The results indicated that harmine inhibited the proliferation MDA-MB231 cells in a dose-dependent manner and markedly suppressed migration and invasion of MDA-MB231 cells. The mechanism involved in part through Notch signaling. The Notch activity was significantly inhibited by harmine treatment and harmine suppressed the expression of Jagged1 which is a key ligand to activate Notch signaling. These findings suggest a novel mechanism of harmine on anti-cancer activity and harmine may act as a potential therapeutic drug for breast cancer treatment.

Effects of Curcuma longa L. on MDA-MB-231 Human Breast Cancer Cells and DMBA-induced Breast Cancer in Rats (울금이 MDA-MB-231 세포 및 DMBA로 유발된 흰쥐의 유방암에 미치는 영향)

  • Yang, Dong-Seon;Yang, Seung-Jeong
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.3
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    • pp.44-58
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    • 2013
  • Objectives: Breast cancer is the most common cancer among women and has rapidly increasing rate annually. At present, western cancer therapies by surgery, radiation, and anticancer drug have not been fully effective. So many interests are given to herbal medicine on cancer treatment recently. This study was designed to investigate the effects of Curcuma longa L. (CL) on MDA-MB-231 human breast cancer cells and DMBA-induced breast cancer in rats. Methods: In this experiment, MDA-MB-231 cells were cultured in cell culture plates. 0.0625, 0.125, 0.25, 0.5, 1.0 mg/ml of CL extract were tested for their anti-proliferative effects on MDA-MB-231 cells by MMT assay. And we induced breast cancer in rats. The changes in tumor's weight, and the effects on proliferations of splenocyte and thymocyte were investigated. Results: CL showed anti-proliferative effects on MDA-MB-231 cells in proportion to concentration of the CL. DMBA-induced breast cancer in rats, tumor's weight of the rat was not statistically significant, but showed a tendency to be reduced in the groups treated with CL. Proliferation rate of the rat's splenocyte and thymocyte increased in proportion to CL. In breast cancer tissue, expression of ER-${\alpha}$ was weakened proportionately to the concentration of the CL. Conclusions: These data suggest that CL can prevent the proliferation of breast cancer, then CL is useful to treat patient with breast cancer.