scholarly journals Aviculin Isolated from Lespedeza cuneata Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1708 ◽  
Author(s):  
Dahae Lee ◽  
Yong Hoon Lee ◽  
Kwang Ho Lee ◽  
Bum Soo Lee ◽  
Akida Alishir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Underlying Mechanism ◽  
Intrinsic Apoptosis ◽  
Lespedeza Cuneata ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Mcf 7

The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from Lespedeza cuneata (Dum. Cours.) G. Don. (Fabaceae) on MCF-7 human breast cancer cells and determine the underlying mechanism. Using the bioassay-guided isolation by water soluble tetrazolium salt (WST-1)-based Ez-Cytox assay, nine compounds (four lignan glycosides (1–4), three flavonoid glycosides (5–7), and two phenolic compounds (8 and 9)) were isolated from the ethyl acetate (EA) fraction of the L. cuneata methanolic extract. Of these, aviculin (2), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC50: 75.47 ± 2.23 μM). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (2) was found to induce apoptotic cell death through the intrinsic apoptosis pathway, as indicated by the increased expression of initiator caspase-9, executioner caspase-7, and poly (ADP-ribose) polymerase (PARP). Aviculin (2)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (2) could induce breast cancer cell apoptosis through the intrinsic apoptosis pathway, and it can therefore be considered an excellent candidate for herbal treatment of breast cancer.

scholarly journals HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1280
Author(s):  
Seung-Ho Park ◽  
Hyunhee Kim ◽  
Sungmin Kwak ◽  
Ji-Hoon Jeong ◽  
Jangho Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Tnf Α ◽  
Mcf 7

Tumor necrosis factor-α (TNF-α) plays a significant role in inflammation and cancer-related apoptosis. We identified a TNF-α-mediated epigenetic mechanism of apoptotic cell death regulation in estrogen receptor-α (ERα)-positive human breast cancer cells. To assess the apoptotic effect of TNF-α, annexin V/ propidium iodide (PI) double staining, cell viability assays, and Western blotting were performed. To elucidate this mechanism, histone deacetylase (HDAC) activity assay and immunoprecipitation (IP) were conducted; the mechanism was subsequently confirmed through chromatin IP (ChIP) assays. Finally, we assessed HDAC3–ERα-mediated apoptotic cell death after TNF-α treatment in ERα-positive human breast cancer (MCF-7) cells via the transcriptional activation of p53 target genes using luciferase assay and quantitative reverse transcription PCR. The TNF-α-induced selective apoptosis in MCF-7 cells was negatively regulated by the HDAC3–ERα complex in a caspase-7-dependent manner. HDAC3 possessed a p53-binding element, thus suppressing the transcriptional activity of its target genes. In contrast, MCF-7 cell treatment with TNF-α led to dissociation of the HDAC3–ERα complex and substitution of the occupancy on the promoter by the p53–p300 complex, thus accelerating p53 target gene expression. In this process, p53 stabilization was accompanied by its acetylation. This study showed that p53-mediated apoptosis in ERα-positive human breast cancer cells was negatively regulated by HDAC3–ERα in a caspase-7-dependent manner. Therefore, these proteins have potential application in therapeutic strategies.

scholarly journals Functional Estrogen Receptors in the Mitochondria of Breast Cancer Cells

2006 ◽  
Vol 17 (5) ◽  
pp. 2125-2137 ◽  
Author(s):  
Ali Pedram ◽  
Mahnaz Razandi ◽  
Douglas C. Wallace ◽  
Ellis R. Levin
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Estrogen Receptors ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Cytoplasmic Organelle ◽  
Cytochrome C Release ◽  
Mitochondrial Functions ◽  
Mcf 7

Steroid hormones have been reported to indirectly impact mitochondrial functions, attributed to nuclear receptor-induced production of proteins that localize in this cytoplasmic organelle. Here we show high-affinity estrogen receptors in the mitochondria of MCF-7 breast cancer cells and endothelial cells, compatible with classical estrogen receptors ERα and ERβ. We report that in MCF-7, estrogen inhibits UV radiation-induced cytochrome C release, the decrease of the mitochondrial membrane potential, and apoptotic cell death. UV stimulated the formation of mitochondrial reactive oxygen species (mROS), and mROS were essential to inducing mitochondrial events of cell death. mROS mediated the UV activation of c-jun N-terminal kinase (JNK), and protein kinase C (PKC) δ, underlying the subsequent translocation of Bax to the mitochondria where oligomerization was promoted. E2 (estradiol) inhibited all these events, directly acting in mitochondria to inhibit mROS by rapidly up-regulating manganese superoxide dismutase activity. We implicate novel functions of ER in the mitochondria of breast cancer that lead to the survival of the tumor cells.

Sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKKβ

APOPTOSIS ◽  
2009 ◽  
Vol 14 (7) ◽  
pp. 913-922 ◽  
Author(s):  
A-Mi Seo ◽  
Seung-Woo Hong ◽  
Jae-Sik Shin ◽  
In-Chul Park ◽  
Nam-Joo Hong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals Doxorubicin resistance mediated by cytoplasmic macrophage colony-stimulating factor is associated with switch from apoptosis to autophagic cell death in MCF-7 breast cancer cells

2016 ◽  
Vol 241 (18) ◽  
pp. 2086-2093 ◽  
Author(s):  
Mengxia Zhang ◽  
Hailiang Zhang ◽  
Fan Tang ◽  
Yuhua Wang ◽  
Zhongcheng Mo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Colony Stimulating Factor ◽  
Doxorubicin Resistance ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Mcf 7

Macrophage colony-stimulating factor is a vital factor in maintaining the biological function of monocyte–macrophage lineage. It is expressed in many tumor tissues and cancer cells. Recent findings indicate that macrophage colony-stimulating factor might contribute to chemoresistance, but the precise mechanisms are unclear. This study was to explore the effect of macrophage colony-stimulating factor on doxorubicin resistance in MCF-7 breast cancer cells and the possible mechanism. In the study, the human breast cancer cells, MCF-7, were transfected with macrophage colony-stimulating factor. We document that cytoplasmic macrophage colony-stimulating factor induces doxorubicin resistance and inhibits apoptosis in MCF-7 cells. Further studies demonstrated that cytoplasmic macrophage colony-stimulating factor-mediated apoptosis inhibition was dependent on the activation of PI3K/Akt/Survivin pathway. More importantly, we found that macrophage colony-stimulating factor-induced autophagic cell death in doxorubicin-treated MCF-7 cells. Taken together, we show for the first time that macrophage colony-stimulating factor-induced doxorubicin resistance is associated with the changes in cell death response with defective apoptosis and promotion of autophagic cell death.

scholarly journals Autocrine Growth Hormone (GH)-Mediated Triptolide Resistance Overcame by Metformin Co-Treatment in MDA-MB231 Breast Cancer Cells Through ER Stress Pathway

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 9
Author(s):  
Amani Abdulmunem ◽  
Pınar Obakan-Yerlikaya ◽  
Elif-Damla Arisan ◽  
Ajda Coker-Gurkan
Keyword(s):  
Breast Cancer ◽  
Growth Hormone ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Autocrine Growth ◽  
Common Cancer

Breast cancer is the most common cancer in women worldwide and the second most common cancer overall. Autocrine growth hormone (GH) expression induced cell proliferation, growth, invasion-metastasis in vitro and in vivo breast cancer models. Moreover, forced GH signaling acts as a drug resistance profile in breast cancer cell lines against chemotherapeutic drugs such as tamoxifen, mitomycin C, doxorubicin and curcumin. Triptolide, an active plant extract from Tripterygium wilfordii, has been shown to induce apoptotic cell death in various cancer cells such a prostate, colon, breast cancer. Metformin, a common therapeutic agent for type II Diabetes mellitus, has been shown to induce autophagy, endoplasmic reticulum (ER) stress and apoptotic cell death in cancer cells. Our aim is to demonstrate the potential effect of metformin on triptolide-mediated drug resistance in autocrine GH expressing MDA-MB-231 breast cancer cells through Endoplasmic reticulum (ER) stress. Autocrine GH-mediated triptolide (20 nM) resistance overcame by metformin (2 mM) co-teatment in MDA-MB231 breast cancer cells through accelerating cell viability loss, growth inhibition compared to alone triptolide treatment. Combined treatment increased apoptotic cell death via CHOP activation, IRE1α upregulation. Consequently, we suggest that triptolide can be more effective with metformin combination in MDA-MB-231 GH+ drug resistant breast cancer cells.

scholarly journals Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and the Bcl-2 Protein Family

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Christopher Platen ◽  
Stephan Dreschers ◽  
Jessica Wappler ◽  
Andreas Ludwig ◽  
Stefan Düsterhöft ◽  
...  
Keyword(s):  
Cell Death ◽  
Bacterial Infections ◽  
Caspase 3 ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Dependent Manner ◽  
Intrinsic Apoptosis ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway

Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphiregulin (AREG) is increasingly expressed on the cell surface of neonatal monocytes, resulting in remarkably higher soluble AREG levels after proteolytic shedding. In this study, we found that E. coli-infected neonatal monocytes show an increased phosphorylation of ERK, increased expression of Bcl-2 and Bcl-XL, and reduced levels of cleaved caspase-3 and caspase-9 compared to adult monocytes. In both cell types, additional stimulation with soluble AREG further increased ERK activation and expression of Bcl-2 and Bcl-XL and reduced levels of cleaved caspase-3 and caspase-9 in an EGFR-dependent manner. These data suggest that reduced PICD of neonatal monocytes could be due to reduced intrinsic apoptosis and that AREG can promote protection against PICD. This reduction of the intrinsic apoptosis pathway in neonatal monocytes could be relevant for severely prolonged inflammatory responses of neonates.

scholarly journals Oncogenic miR-20b-5p contributes to malignant behaviors of breast cancer stem cells by bidirectionally regulating CCND1 and E2F1

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Liqin Xia ◽  
Feng Li ◽  
Jun Qiu ◽  
Zhongming Feng ◽  
Zihan Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Wound Healing ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Breast Cancer Stem Cells ◽  
Xenograft Growth ◽  
Mcf 7

Abstract Background Breast cancer is the leading cause of cancer mortality in women worldwide. Therefore, it is of great significance to identify the biological mechanism of tumorigenesis and explore the development of breast cancer to achieve a better prognosis for individuals suffering from breast cancer. MicroRNAs (miRNAs) have become a hot topic in cancer research, but the underlying mechanism of its involvement in cancer remains unclear. Methods The miRNA profile between breast cancer stem cells (BCSCs, CD44+CD24−/low) and control MCF-7 breast cancer cells was obtained in a previous study. Based on biological analysis, miR-20b-5p was hypothesized to be a key factor due to the malignant behavior of BCSCs. Then, agomir-20b-5p and antagomir-20b-5p were transfected into MCF-7 and T47D breast cancer cells to detect cell migration, wound healing and proliferation, and lentivirus vectors silencing or overexpressing miR-20b-5p were transfected into T47D-CSCs to detect proliferation and apoptosis. The effect of miR-20b-5p on xenograft growth was investigated in vivo by transfection of a lentivirus-overexpression vector into T47D cells. The target genes were predicted by the online programs picTar, miRanda and TargetScan and verified by dual luciferase assay, and changes in protein expression were detected by western blot. Results MiR-20b-5p had the highest degree in both the miRNA-gene network and miRNA-GO network to regulate BCSCs. Overexpression of miR-20b-5p significantly promoted the migration and wound healing ability of MCF-7 cells and T47D cells compared with the control (P < 0.05). In addition, miR-20b-5p facilitated the proliferation of MCF-7 cells and T47D-CSCs (P < 0.05) and inhibited the apoptosis of T47D-CSCs (P < 0.05). Moreover, miR-20b-5p promoted xenograft growth compared with the control group (P < 0.05). Accordingly, potential targets of both CCND1 and E2F1 were predicted by bioinformatics analysis. MiR-20b-5p directly targeted both CCND1 and E2F1 in a dual luciferase assay, while antagomir-20b-5p downregulated the protein levels of CCND1 and E2F1. Conclusions Oncogenic miR-20b-5p was confirmed to promote the malignant behaviors of breast cancer cells and BCSCs. The underlying mechanism lies in that miR-20b-5p overall enhanced both CCND1 and E2F1 targets via bidirectional regulation probably involving direct downregulation and indirect upregulation.

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