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

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
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.

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

Nutrients ◽  
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.

scholarly journals Ginsenoside Rg1 Induces Apoptotic Cell Death in Triple-Negative Breast Cancer Cell Lines and Prevents Carcinogen-Induced Breast Tumorigenesis in Sprague Dawley Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yan Chu ◽  
Wentao Zhang ◽  
G. Kanimozhi ◽  
G. R. Brindha ◽  
Defu Tian
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Apoptotic Cell ◽  
Experimental Models ◽  
Apoptotic Cell Death ◽  
Breast Cancer Cell Lines ◽  
Ginsenoside Rg1

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.

scholarly journals Neuroprotective Effects of Alpha-Mangostin on MPP+-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Prachya Janhom ◽  
Permphan Dharmasaroja
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Caspase 3 ◽  
Nuclear Dna ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Concomitant Treatment ◽  
Ros Production ◽  
Cellular Models ◽  
Induced Apoptosis

In vitrostudies have shown that extracts from mangosteen (Garcinia mangostanaLinn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson’s disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP+-induced apoptosis. The effects of alpha-mangostin on MPP+-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP+on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP+. Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP+. The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP+treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP+-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.

Cytotoxic potential of dispirooxindolo/acenaphthoquino andrographolide derivatives against MCF-7 cell line

MedChemComm ◽  
2015 ◽  
Vol 6 (4) ◽  
pp. 702-707 ◽  
Author(s):  
Debanjana Chakraborty ◽  
Arindam Maity ◽  
Chetan K. Jain ◽  
Abhijit Hazra ◽  
Yogesh P. Bharitkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Line ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cytotoxic Potential ◽  
Cell Death Pathway ◽  
Line P ◽  
Mcf 7

Dispiro andrographolides induce a caspase-dependent apoptotic cell death pathway in breast cancer (MCF-7) cells.

scholarly journals Ricinus communis Butanol Fraction Inhibits MCF-7 Breast Cancer Cell Migration, Adhesion, and Invasiveness

2021 ◽  
Vol 20 ◽  
pp. 153473542097768
Author(s):  
Rixile Mabasa ◽  
Kholofelo Malemela ◽  
Karabo Serala ◽  
Mante Kgakishe ◽  
Thabe Matsebatlela ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Migration ◽  
Cell Viability ◽  
Apoptotic Cell ◽  
Ricinus Communis ◽  
Gelatin Zymography ◽  
Apoptotic Cell Death ◽  
Butanol Fraction ◽  
Mcf 7

In this study, the potential of an n-butanol fraction from Ricinus communis to prevent metastasis in MCF-7 breast cancer cells was investigated. The effect of the fraction on BUD-8 and MCF-7 cell viability was assessed using the MTT assay. Apoptotic cell death was analyzed by Hoechst staining assay. The antimetastatic effect of the fraction on MCF-7 cell was evaluated using the wound healing, adhesion and Boyden chamber invasion assays. Gelatin-zymography was used to assess the effect of the fraction on MMP-2 and MMP-9 activity. The expression profile of proteins implicated in metastasis and angiogenesis was determined using the human angiogenesis antibody array kit, following treatment with the fraction. BUD-8 cell viability was significantly reduced at concentrations between 300 and 500 µg/ml of the extract. In contrast, a significant reduction in cell viability was seen in MCF-7 cells treated with 400 to 500 µg/ml of the fraction. At sub-lethal concentrations (100 and 200 µg/ml) of the fraction, no nuclei morphological changes associated with apoptotic cell death were observed in MCF-7 cells. In addition, the fraction showed to have an inhibitory effect on MCF-7 cell migration, adhesion, invasiveness, and MMP-2 activity. Moreover, the fraction was seen to modulate the expression of several proteins, such as MMP-9, uPA, VEGF, and TGF-β1, playing a role in the metastasis process. This study demonstrates that the n-butanol fraction of R. communis can inhibit major steps of the metastatic cascade and modulate metastasis regulatory proteins. Thus, the fraction can be considered a potential source of antimetastatic agents that could be useful in the treatment of malignant cancers.

Sign in / Sign up

Export Citation Format

Share Document