Abstract 2119: Acetylated secretory APE1/Ref-1 induces apoptotic cell death in orthotopic xenografts of triple-negative breast cancer

The objective of this study is to investigate the anticancer potential of ginsenoside Rg1 using in vitro and in vivo experimental models. In this study, we found that ginsenoside Rg1 induces cytotoxicity and apoptotic cell death through reactive oxygen species (ROS) generation and alterations in mitochondrial membrane potential (MMP) in the triple-negative breast cancer cells (MDA-MB-MD-231 cell lines). We found that ginsenoside Rg1 induces the formation of gamma H2AX foci, an indication of DNA damage, and subsequent TUNEL positive apoptotic nuclei in the MDA-MB-MD-231 cell lines. Further, we found that ginsenoside Rg1 prevents 7,12-dimethylbenz (a) anthracene (DMBA; 20 mg/rat) induced mammary gland carcinogenesis in experimental rats. We observed oral administration of ginsenoside Rg1 inhibited the DMBA-mediated tumor incidence, prevented the elevation of oxidative damage markers, and restored antioxidant enzymes near to normal. Furthermore, qRT-PCR gene expression studies revealed that ginsenoside Rg1 prevents the expression of markers associated with cell proliferation and survival, modulates apoptosis markers, downregulates invasion and angiogenesis markers, and regulates the EMT markers. Therefore, the present results suggest that ginsenoside Rg1 shows significant anticancer properties against breast cancer in experimental models.

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Substance P Receptor Signaling Mediates Doxorubicin-Induced Cardiomyocyte Apoptosis and Triple-Negative Breast Cancer Chemoresistance

BioMed Research International ◽

10.1155/2016/1959270 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 19

Author(s):

Prema Robinson ◽

Moses Kasembeli ◽

Uddalak Bharadwaj ◽

Nikita Engineer ◽

Kris T. Eckols ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Substance P ◽

Cell Viability ◽

Cell Line ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Ros Production

Doxorubicin (DOX), an anthracycline, is broadly considered the most active single agent available for treating breast cancer but has been known to induce cardiotoxicity. Although DOX is highly effective in treating triple-negative breast cancer (TNBC), DOX can have poor outcomes owing to induction of chemoresistance. There is an urgent need to develop new therapies for TNBC aimed at improving DOX outcome and DOX-induced cardiotoxicity. Substance P (SP), a neuropeptide involved in pain transmission is known to stimulate production of reactive oxygen species (ROS). Elevated cardiac ROS is linked with heart injury and failure. We investigated the role of SP in chemotherapy-associated death of cardiomyocytes and chemoresistance. We showed that pretreating a cardiomyocyte cell line (H9C2) and a TNBC cell line (MDA-MB 231) with aprepitant, a SP receptor antagonist that is routinely used to treat chemotherapy-associated associated nausea, decreased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in cardiomyocytes and increased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in TNBC cells compared with cells treated with DOX alone. Our findings demonstrate the ability of aprepitant to decrease DOX-induced killing of cardiomyocytes and to increase cancer cell sensitivity to DOX, which has tremendous clinical significance.

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St. John’s Wort Suppresses Growth in Triple-Negative Breast Cancer Cell Line MDA-MB-231 by Inducing Prodeath Autophagy and Apoptosis

Nutrients ◽

10.3390/nu12103175 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3175

Author(s):

Mikyoung You ◽

Young-Hyun Lee ◽

Hwa-Jin Kim ◽

Ji Hyun Kook ◽

Hyeon-A Kim

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cell Line ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Apoptotic Cell ◽

Cancer Cell Line ◽

Dependent Manner ◽

St John’S Wort ◽

St John's Wort

The rational regulation of programmed cell death by means of autophagy and apoptosis has been considered a potential treatment strategy for cancer. We demonstrated the inhibitory effect of St. John’s Wort (SJW) on growth in the triple-negative breast cancer (TNBC) cell line and xenografted mice and its target mechanism concerning autophagic and apoptotic cell death. SJW ethanol extract (SJWE) inhibited proliferation in a dose-dependent manner. SJWE treatment dramatically increased autophagy flux and apoptosis compared with the control. The autophagy inhibitor, 3-methyladenine (3-MA), reversed the SJWE-induced inhibition of cell proliferation and regulation of autophagy and apoptosis, indicating that SJWE induced apoptosis through prodeath autophagy. Furthermore, SJWE inhibited tumor growth and induced autophagy and apoptosis in the tumor of MDA-MB-231 xenografted athymic nude mice. Our results indicate that SJWE might have great potential as a new anticancer therapy for triple-negative breast cancer by inducing prodeath autophagy and apoptosis.

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Abstract 3795: Cardiac glycoside digitoxin and its monosaccharide analogue MonoD inhibit NFκB to induce apoptotic cell death in ER+ MCF7 and triple-negative MDAMB-468 breast cancer cells

10.1158/1538-7445.am2015-3795 ◽

2015 ◽

Author(s):

Yogesh Kulkarni ◽

Vivek Kaushik ◽

Raj Venkatadri ◽

Clayton Wright ◽

Juan Sebastian Yakisich ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Cardiac Glycoside ◽

Breast Cancer Cells ◽

Triple Negative ◽

Apoptotic Cell ◽

Apoptotic Cell Death

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DSTYK Enhances Chemoresistance in Triple-Negative Breast Cancer Cells

Cells ◽

10.3390/cells11010097 ◽

2021 ◽

Vol 11 (1) ◽

pp. 97

Author(s):

Stella C. Ogbu ◽

Samuel Rojas ◽

John Weaver ◽

Phillip R. Musich ◽

Jinyu Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Apoptotic Cell ◽

Breast Cancer Patients ◽

Tumor Cell Death ◽

Drug Induced ◽

Orthotopic Mouse Model ◽

Cellular Models

Breast cancer, as the most prevalent cancer in women, is responsible for more than 15% of new cancer cases and about 6.9% of all cancer-related death in the US. A major cause of therapeutic failure in breast cancer is the development of resistance to chemotherapy, especially for triple-negative breast cancer (TNBC). Therefore, how to overcome chemoresistance is the major challenge to improve the life expectancy of breast cancer patients. Our studies demonstrate that TNBC cells surviving the chronic treatment of chemotherapeutic drugs show significantly higher expression of the dual serine/threonine and tyrosine protein kinase (DSTYK) than non-treated parental cells. In our in vitro cellular models, DSTYK knockout via the CRISPR/Cas9-mediated technique results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, DSTYK knockout promotes chemotherapeutic drug-induced tumor cell death in an orthotopic mouse model. These findings suggest that DSTYK exerts an important and previously unknown role in promoting chemoresistance. Our studies provide fundamental insight into the role of DSTYK in chemoresistance in TNBC cells and lay the foundation for the development of new strategies targeting DSTYK for improving TNBC therapy.

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Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins

Scientific Reports ◽

10.1038/s41598-021-89420-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mohsin Ali Khan ◽

Sahabjada Siddiqui ◽

Imran Ahmad ◽

Romila Singh ◽

Durga Prasad Mishra ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Mononuclear Cells ◽

Apoptotic Cell ◽

Human Peripheral Blood ◽

Annexin V ◽

Phoenix Dactylifera ◽

Mtor Pathway ◽

Peripheral Blood Mononuclear

AbstractAjwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC–MS) and investigated anticancer effects against MDA-MB-231 cells. LC–MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.

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