Simvastatin induces apoptosis in human breast cancer cells in a NFκB-dependent manner and abolishes the anti-apoptotic signaling of TF/FVIIa and TF/FVIIa/FXa

Natural products have proved to be a promising source for the development of potential anticancer drugs. Emodin, a natural compound from Rheum palmatum, is used to treat several types of cancers, including lung, liver, and pancreatic. However, there are few reports regarding its use in the treatment of breast cancer. Thus, the therapeutic effect and mechanism of emodin on MCF-7 human breast cancer cells were investigated in this study. Morphological observations and cell viability were evaluated to determine the anti-proliferation activity of emodin. Network pharmacology and molecular docking were performed to screen the potential targets. Western blot analysis was used to explore a potential antitumor mechanism. The results showed that emodin (50–100 μmol/L) could significantly inhibit the proliferation of MCF-7 cells in a time and dose-dependent manner. Furthermore, virtual screening studies indicated that emodin was a potent aryl hydrocarbon receptor (AhR) agonist in chemotherapy for breast cancer. Finally, when MCF-7 cells were treated with emodin (100 μmol/L) for 24 h, the AhR and cytochrome P450 1A1 (CYP1A1) protein expression levels were significantly upregulated compared with the control group. Our study indicated that emodin exhibited promising antitumor activity in MCF-7 cells, likely through activation of the AhR-CYP1A1 signaling pathway. These findings lay a foundation for the application of emodin in breast cancer treatment.

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RRR-γ-tocopherol induces human breast cancer cells to undergo apoptosis via death receptor 5 (DR5)-mediated apoptotic signaling

Cancer Letters ◽

10.1016/j.canlet.2007.10.008 ◽

2008 ◽

Vol 259 (2) ◽

pp. 165-176 ◽

Cited By ~ 24

Author(s):

Weiping Yu ◽

Sook-Kyung Park ◽

Li Jia ◽

Richa Tiwary ◽

Wenjun W. Scott ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Death Receptor ◽

Death Receptor 5 ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Apoptotic Signaling

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Arctigenin Enhances the Cytotoxic Effect of Doxorubicin in MDA-MB-231 Breast Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21082997 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2997 ◽

Cited By ~ 2

Author(s):

Kyu-Shik Lee ◽

Min-Gu Lee ◽

Yun-Suk Kwon ◽

Kyung-Soo Nam

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Nuclear Translocation ◽

Dependent Manner ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Concentration Dependent Manner

Several reports have described the anti-cancer activity of arctigenin, a lignan extracted from Arctium lappa L. Here, we investigated the effect of arctigenin (ATG) on doxorubicin (DOX)-induced cell death using MDA-MB-231 human breast cancer cells. The results showed that DOX-induced cell death was enhanced by ATG/DOX co-treatment in a concentration-dependent manner and that this was associated with increased DOX uptake and the suppression of multidrug resistance-associated protein 1 (MRP1) gene expression in MDA-MB-231 cells. ATG enhanced DOX-induced DNA damage and decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expressions of RAD51 and survivin. Cell death caused by ATG/DOX co-treatment was mediated by the nuclear translocation of apoptosis inducing factor (AIF), reductions in cellular and mitochondrial Bcl-2 and Bcl-xL, and increases in mitochondrial BAX levels. However, caspase-3 and -7 did not participate in DOX/ATG-induced cell death. We also found that DOX/ATG-induced cell death was linked with activation of the p38 signaling pathway and suppressions of the phosphorylations and expressions of Akt and c-Jun N-terminal kinase. Taken together, these results show that ATG enhances the cytotoxic activity of DOX in MDA-MB-231 human breast cancer cells by inducing prolonged p21 expression and p38-mediated AIF-dependent cell death. In conclusion, our findings suggest that ATG might alleviate the side effects and improve the therapeutic efficacy of DOX.

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Oridonin Induces Apoptosis, Inhibits Migration and Invasion on Highly-Metastatic Human Breast Cancer Cells

The American Journal of Chinese Medicine ◽

10.1142/s0192415x13500134 ◽

2013 ◽

Vol 41 (01) ◽

pp. 177-196 ◽

Cited By ~ 73

Author(s):

Shengpeng Wang ◽

Zhangfeng Zhong ◽

Jianbo Wan ◽

Wen Tan ◽

Guosheng Wu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Dependent Manner ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Integrin Β1 ◽

Mcf 7

Oridonin, a natural tetracycline diterpenoid isolated from Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide variety of tumors. However, its effect on highly metastatic breast cancer cells has not been addressed. In this study, we investigated the effects of oridonin on growth, migration and invasion of highly-metastatic human breast cancer cells. Our results showed that oridonin induced potent growth inhibition on human breast cancer cells MCF-7 and MDA-MB-231 in a time- and dose-dependent manner. According to the flow cytometric analysis, oridonin suppressed MCF-7 cell growth by cell cycle arrest at the G2/M phase and caused accumulation of MDA-MB-231 cells in the Sub-G1 phase. The induced apoptotic effect of oridonin was further confirmed by a morphologic characteristics assay and TUNEL assay. Oridonin triggered the reduction of Bcl-2/Bax ratio, caspase-8, NF-κB (p65), IKKα, IKKβ, phospho-mTOR, and increased expression level of cleaved PARP, Fas and PPARγ in a time-dependent manner. Immunofluorescent analysis showed that γH2AX-containing nuclear foci were significant in oridonin-treated MDA-MB-231 cells. Meanwhile, oridonin significantly suppressed MDA-MB-231 cell migration and invasion, decreased MMP-2/MMP-9 activation and inhibited the expression of Integrin β1 and FAK. In conclusion, oridonin inhibited the growth and induced apoptosis in breast cancer cells, which might be related to DNA damage and activation of intrinsic or extrinsic apoptotic pathways. Moreover, oridonin also inhibited tumor invasion and metastasis in vitro possibly via decreasing the expression of MMPs and regulating the Integrin β1/FAK pathway in MDA-MB-231 cells.

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