scholarly journals xCT-Driven Expression of GPX4 Determines Sensitivity of Breast Cancer Cells to Ferroptosis Inducers

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 317
Author(s):  
Namgyu Lee ◽  
Anne E. Carlisle ◽  
Austin Peppers ◽  
Sung Jin Park ◽  
Mihir B. Doshi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Expression Levels ◽  
Selenium Uptake ◽  
Cancer Tissues ◽  
Potential Therapeutics

Inducers of ferroptosis such as the glutathione depleting agent Erastin and the GPX4 inhibitor Rsl-3 are being actively explored as potential therapeutics in various cancers, but the factors that determine their sensitivity are poorly understood. Here, we show that expression levels of both subunits of the cystine/glutamate antiporter xCT determine the expression of GPX4 in breast cancer, and that upregulation of the xCT/selenocysteine biosynthesis/GPX4 production axis paradoxically renders the cancer cells more sensitive to certain types of ferroptotic stimuli. We find that GPX4 is strongly upregulated in a subset of breast cancer tissues compared to matched normal samples, and that this is tightly correlated with the increased expression of the xCT subunits SLC7A11 and SLC3A2. Erastin depletes levels of the antioxidant selenoproteins GPX4 and GPX1 in breast cancer cells by inhibiting xCT-dependent extracellular reduction which is required for selenium uptake and selenocysteine biosynthesis. Unexpectedly, while breast cancer cells are resistant compared to nontransformed cells against oxidative stress inducing drugs, at the same time they are hypersensitive to lipid peroxidation and ferroptosis induced by Erastin or Rsl-3, indicating that they are ‘addicted’ to the xCT/GPX4 axis. Our findings provide a strategic basis for targeting the anti-ferroptotic machinery of breast cancer cells depending on their xCT status, which can be further explored.

scholarly journals miR-17-5p Combined with Epirubicin Inhibits the Progression of Breast Cancer Cells

2020 ◽  
Author(s):  
Lingling Zhao ◽  
Zhongjian Zhu ◽  
Jiang Du ◽  
Yuanyu Zhao ◽  
Dandan Fan
Keyword(s):  
Breast Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Rt Pcr ◽  
Expression Levels ◽  
Cancer Tissues ◽  
Mcf 7

Abstract Background: Breast cancer is the most common malignant tumor for women, which has been ranked first in women’ s cancer-related death. The objectives of the study are to uncover the underlying mechanisms of combination therapy of epirubicin with miR-17-5p in breast cancer. Methods: The expression levels of miR-17-5p were determined by quantitative RT-PCR. The survival rate of MCF-7 cell was detected respectively by MTT assay. The expression levels of miR-17-5p in MCF-7 cell was tested respectively with Ep via quantitative RT-PCR. miR-17-5p was to be transected with miR-17-5p mimic and negative control of miR-17-5p mimic (NC). Quantitative RT-PCR, MTT assay, flow cytometry assay, western blot for the proliferation and apoptosis related proteins were performed to determine the function of miR-17-5p in breast cancer cells. The bioinformatic programs TargetScan was used to predict the targets for miR-17-5p. Luciferase reporter gene assay system was used to validate and determine the targets of miR-17-5p. The relation between targets protein levels in breast cancer cells was investigated by western blot. Results: The expression levels of miR-17-5p was associated with the breast cancer tissues. The levels of miR-17-5p was down-regulated in breast cancer tissues and cells. Ep could inhibit viability of cancer cells in a concentration dependent manner and promote the expression of miR-17-5p in breast cancer cell lines. Over-expression of miR-17-5p induced cell apoptosis and upregulated the expression of p53, p21 and p27. miR-17-5p co-cultured with Ep is better than the other groups. The relative luciferase activity revealed that STAT3 was a potential target gene of miR-17-5p. Conclusions: Our work will prove that epirubicin regulated the expression of miR-17-5p to strengthen this effect of epirubicin and inhibited the progression of breast cancer.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saber Yari Bostanabad ◽  
Senem Noyan ◽  
Bala Gur Dedeoglu ◽  
Hakan Gurdal
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Function ◽  
Expression Profiles ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Cycle Genes

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

2021 ◽  
pp. 096032712198942
Author(s):  
Xiaoxue Zhang ◽  
Xianxin Xie ◽  
Kuiran Gao ◽  
Xiaoming Wu ◽  
Yanwei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

Antitumor Action of Amygdalin on Human Breast Cancer Cells by Selective Sensitization to Oxidative Stress

2018 ◽  
Vol 71 (3) ◽  
pp. 483-490 ◽  
Author(s):  
Muayad Mehdi Abboud ◽  
Wajdy Al Awaida ◽  
Hakam Hasan Alkhateeb ◽  
Asia Numan Abu-Ayyad
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Antitumor Action ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals MicroRNA let-7g directly targets forkhead box C2 (FOXC2) to modulate bone metastasis in breast cancer

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Lei Wang ◽  
Ming Li ◽  
Yongxin Zhou ◽  
Yu Zhao
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Bone Metastasis ◽  
Western Blot ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Qrt Pcr ◽  
Forkhead Box ◽  
Novel Target ◽  
Cancer Tissues

AbstractAberrantly expressed microRNAs have been implicated in lots of cancers. Reduced amounts of let-7g have been found in breast cancer tissues. The function of let-7g in bone metastasis of breast cancer remains poorly understood. This study is to explore the significance of let-7g and its novel target gene in bone metastasis of breast cancer.The expression of let-7g or forkhead box C2 (FOXC2) was measured in human clinical breast cancer tissues with bone metastasis by using quantitative real-time Polymerase Chain Reaction (qRT-PCR). After transfection with let-7g or anti-let-7g in breast cancer cell linesMDA-MB-231or SK-BR3, qRT-PCR and Western blot were done to test the levels of let-7g and FOXC2. The effect of anti-let-7g and/ or FOXC2 RNA interference (RNAi) on cell migration in breast cancer cells was evaluated by using wound healing assay.Clinically, qRT-PCR showed that FOXC2 levels were higher in breast cancer tissues with bone metastasis than those in their noncancerous counterparts. Let-7g was showed to be negatively correlated with FOXC2 in human breast cancer samples with bone metastasis. We found that enforced expression of let-7g reduced levels of FOXC2 protein by using Western blot in MDA-MB-231 cells. Conversely, anti-let-7g enhanced levels of FOXC2 in SK-BR3 cells. In terms of function, anti-let-7g accelerated migration of SK-BR3 cells. Interestingly, FOXC2 RNAi abrogated anti-let-7g-mediated migration in breast cancer cells. Thus, we conclude that let-7g suppresses cell migration through targeting FOXC2 in breast cancer. Our finding provides a new perspective for understanding the mechanism of bone metastasis in breast cancer.

Oxidative Stress in Caffeine Action on the Proliferation and Death of Human Breast Cancer Cells MCF-7 and MDA-MB-231

2020 ◽  
pp. 1-11
Author(s):  
Kaliana Larissa Machado ◽  
Poliana Camila Marinello ◽  
Thamara Nishida Xavier Silva ◽  
Cássio Fernando Nunes Silva ◽  
Rodrigo Cabral Luiz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

scholarly journals Nanostructured Dihydroartemisinin Plus Epirubicin Liposomes Enhance Treatment Efficacy of Breast Cancer by Inducing Autophagy and Apoptosis

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 804 ◽  
Author(s):  
Ying-Jie Hu ◽  
Jing-Ying Zhang ◽  
Qian Luo ◽  
Jia-Rui Xu ◽  
Yan Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapeutic Strategy ◽  
Beclin 1 ◽  
Type I ◽  
Programmed Death ◽  
Cancer Tissues

The heterogeneity of breast cancer and the development of drug resistance are the relapse reasons of disease after chemotherapy. To address this issue, a combined therapeutic strategy was developed by building the nanostructured dihydroartemisinin plus epirubicin liposomes. Investigations were performed on human breast cancer cells in vitro and xenografts in nude mice. The results indicated that dihydroartemisinin could significantly enhance the efficacy of epirubicin in killing different breast cancer cells in vitro and in vivo. We found that the combined use of dihydroartemisinin with epirubicin could efficiently inhibit the activity of Bcl-2, facilitate release of Beclin 1, and further activate Bax. Besides, Bax activated apoptosis which led to the type I programmed death of breast cancer cells while Beclin 1 initiated the excessive autophagy that resulted in the type II programmed death of breast cancer cells. In addition, the nanostructured dihydroartemisinin plus epirubicin liposomes prolonged circulation of drugs, and were beneficial for simultaneously delivering drugs into breast cancer tissues. Hence, the nanostructured dihydroartemisinin plus epirubicin liposomes could provide a new therapeutic strategy for treatment of breast cancer.

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