scholarly journals The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-Dependent YAP Pathway

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6028 ◽  
Author(s):  
Su-Lim Kim ◽  
Hack Sun Choi ◽  
Ji-Hyang Kim ◽  
Dong-Sun Lee
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Underlying Mechanism ◽  
Tissue Growth ◽  
New Approach ◽  
Ru 486 ◽  
Mammosphere Formation ◽  
Cysteine Rich Protein ◽  
Anti Cancer ◽  
Interfering Rna

Ciclesonide is an FDA-approved glucocorticoid used to treat asthma and allergic rhinitis. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying mechanism. Here, we showed that ciclesonide inhibits breast cancer and CSC formation. Similar glucocorticoids—dexamethasone and prednisone—did not inhibit CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays an important role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagonist RU-486 also inhibited CSC formation. Ciclesonide reduced the protein level of the Hippo transducer Yes-associated protein (YAP). GR siRNA induced a decrease in YAP protein expression and inhibited mammosphere formation. The YAP inhibitor verteporfin inhibited CSC formation and transcription of the connective tissue growth factor and cysteine-rich protein 61 genes. The GR/YAP1 pathway regulated breast CSC formation. We showed that the GR/YAP signaling pathway regulates breast CSC formation and revealed a new approach for targeting GR and YAP to inhibit CSC formation.

scholarly journals The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-dependent YAP Pathway

2020 ◽  
Author(s):  
Su-Lim Kim ◽  
Hack Sun Choi ◽  
Ji-Hyang Kim ◽  
Dong-Sun Lee
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Signaling Pathway ◽  
Tissue Growth ◽  
New Approach ◽  
Ru 486 ◽  
Mammosphere Formation ◽  
Anti Cancer ◽  
Aldefluor Assay ◽  
Interfering Rna

Abstract Background Ciclesonide is an inhaled corticosteroid used to treat mild-to-severe asthma. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on studying the effect on breast cancer and breast CSCs by ciclesonide and determining its molecular mechanism. Methods The sensitivity of breast cancer by ciclesonide was determined by cell apoptosis, migration, colony formation, and xenograft. Effect of ciclesonide on CSC formation through GR/YAP pathway was determined by SiRNA of GR and YAP, GR degradation assay, GR antagonist, nuclear localization of GR and YAP, and YAP inhibitor. CSC subpopulation was determined by mammosphere culture, CD44+/CD24-, and aldefluor assay. Results Here, we showed that ciclesonide inhibits breast cancer and CSC growth. Similar glucocorticoids (GC), dexamethasone (DEX) and prednisone, did not suppress CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays a crucial role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagonist RU-486 also inhibited CSC formation. Ciclesonide reduced the protein level of the Hippo transducer Yes-associated protein (YAP). GR siRNA induced a decrease in YAP protein expression and inhibited mammosphere formation. The YAP inhibitor verteporfin inhibited CSC formation and transcription of the connective tissue growth factor and cysteine-rich protein 61 genes. The GR/YAP1 pathway regulated breast CSC formation. Conclusions We describe that ciclesonide inhibition CSCs through GR and YAP signaling pathway. These findings suggest that the GR/YAP signaling pathway regulates breast CSC formation and revealed a new approach for targeting GR and YAP to inhibit CSC formation.

Elaborating the Role of Natural Products on the Regulation of Autophagy and their Potentials in Breast Cancer Therapy

2018 ◽  
Vol 18 (3) ◽  
pp. 239-255 ◽  
Author(s):  
Xunian Zhou ◽  
Grace Gar-Lee Yue ◽  
Stephen Kwok-Wing Tsui ◽  
Jianxin Pu ◽  
Kwok-Pui Fung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Natural Products ◽  
Malignant Tumors ◽  
Underlying Mechanism ◽  
Lysosomal Hydrolases ◽  
Potential Implication ◽  
Growth And Survival ◽  
Protein Levels ◽  
Cancer Breast ◽  
Anti Cancer

Autophagy is an intracellular lysosomal/vacuolar degradation system, in which the inner cytoplasmic cell membrane is degraded by the lysosomal hydrolases, followed by the resulting products released back into the cytosol. It is involved in many physiological processes which are crucial for cell growth and survival. However, disturbance in the autophagic process is often associated with a variety of human diseases, such as cancer. Breast cancer is one of the most malignant tumors characterized by the imbalanced cell proliferation, apoptosis as well as disordered autophagy regulation. The alterations of autophagy related genes or protein levels in breast cancer cells also suggested a potential implication of autophagy in breast cancer development and progression. Many natural products had been reported as potential anti-cancer agents or being considered as direct or indirect sources of new chemotherapy adjuvants to enhance the efficacy or to ameliorate the side effects through the modulation of autophagy. Investigation of the underlying mechanism of these compounds could be crucial for the development of new therapeutic or chemopreventive options for breast cancer treatment. In this review, a summary of those natural products that can regulate autophagy in breast cancer is presented and the potential value of such autophagy modulators on the development of anti-cancer drugs is also discussed.

scholarly journals Activation Ferroptosis Enhanced the Therapy Sensitivity of TNBC to Paclitaxel Via NCOA4 Mediated Ferritinophagy

2021 ◽  
Author(s):  
Yu Qiu ◽  
Qifeng Yu ◽  
Meng Ji ◽  
Zhiwei Zhang ◽  
Liuyun Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Underlying Mechanism ◽  
Breast Cancer Patients ◽  
First Line ◽  
Chemotherapy Drugs ◽  
Regulated Cell Death ◽  
Main Challenge ◽  
Anti Cancer ◽  
New Type ◽  
Line Drug

Abstract BackgroundPaclitaxel (PTX) is the first-line drug for chemotherapy, but Triple-Negative Breast Cancer (TNBC) develops resistance to PTX is the main challenge in clinical therapy. Ferroptosis is a new type of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation accumulation, despite activation of ferroptosis has been shown to enhance the sensibility of tumor to chemotherapy drugs, the underlying mechanism remains unclear. MethodsC11-BODIPY probe and real time PCR was used to detect the ferroptosis level in breast cancer cells. FerroOrange probe and western blot was employed to measure ferritinophagy. The cell viability was examined by CCK-8, EdU and AM/PI double staining.ResultsThe anti-cancer effect of PTX was related to the induction of ferroptosis in TNBC cells, the ferroptosis occurring was mediated by NCOA4-driven ferritinophagy, and the autophagy-related molecules also downregulated in clinical specimens. Furtherly, TNBC cells survival was decreased more significantly than PTX alone when combining with ferroptosis agonist RSL3. In addition, we also discovered that HERC2, a unique identified E3 ubiquitin ligase of NCOA4, obviously expressed downregulation under PTX treated TNBC cells while elevated in breast carcinoma comparing with adjacent tissues. Meanwhile, bioinformatics results showed that the survival rate was significantly lower in breast cancer patients with high expression of HERC2.ConclusionsFerroptosis agonist can assist PTX to enhance the sensitivity of TNBC to PTX in chemotherapy, which possible mechanism is prompting the expression of NCOA4 and the occurrence of ferritinophagy.

scholarly journals SR-B1-targeted nanodelivery of anti-cancer agents: a promising new approach to treat triple-negative breast cancer

2017 ◽  
Vol Volume 9 ◽  
pp. 383-392 ◽  
Author(s):  
Rebecca Johnson ◽  
Nirupama Sabnis ◽  
Xiangle Sun ◽  
Ruhani Ahluwalia ◽  
Andras Lacko
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
New Approach ◽  
Anti Cancer

Molecular Mechanisms of Thymoquinone as Anticancer agent

2020 ◽  
Vol 23 ◽  
Author(s):  
Fatma Ismail Alhmied ◽  
Ali Hassan Alammar ◽  
Bayan Mohammed Alsultan ◽  
Marooj Alshehri ◽  
Faheem Hyder Pottoo
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Human Breast Cancer ◽  
Phase Cell ◽  
Cycle Phase ◽  
Human Breast ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
Anti Cancer

Abstract:: Thymoquinone (TQ), the bioactive constituent of Nigella Sativa seeds is a well-known natural compound for the management of several types of cancers. The anti-cancer properties of thymoquinone are thought to be operated via intervening with various oncogenic pathways including cell cycle arrest, prevention of inflammation and oxidative stress, induction of invasion, metastasis, inhibition of angiogenesis, and apoptosis. As well as up-regulation and down-regulation of specific tumor suppressor genes and tumor promoting genes, respectively. Proliferation of various tumor cells is inhibited by TQ via induction of cell cycle arrest, disruption of the microtubule organization, and down regulating cell survival protein expression. TQ induces G1 phase cell cycle arrest in human breast cancer, colon cancer and osteosarcoma cells through inhibiting the activation of cyclin E or cyclin D and up-regulating p27and p21 a cyclin dependent kinase (Cdk) inhibitor. TQ concentration is a significant factor in targeting a particular cell cycle phase. While high concentration of TQ induced G2 phase arrest in human breast cancer (MCF-7) cells, low concentration causes S phase arrest. This review article provides mechanistic insights into the anti-cancer properties of thymoquinone.

Recent Advances on Therapeutic Peptides for Breast Cancer Treatment

2020 ◽  
Vol 21 ◽  
Author(s):  
Samad Beheshtirouy ◽  
Farhad Mirzaei ◽  
Shirin Eyvazi ◽  
Vahideh Tarhriz
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Specific Binding ◽  
High Specificity ◽  
The Novel ◽  
Anti Cancer ◽  
Therapeutic Peptides ◽  
Low Toxicity

: Breast cancer is a heterogeneous malignancy which is the second cause of mortality among women in the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapies approaches for the treatment of the malignancy. Among the novel methods, therapeutic peptides which target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acids monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides such as specific binding on tumor cells surface, low molecular weight and low toxicity on normal cells make the peptides as an appealing therapeutic agents against solid tumors, particularly breast cancer. Also, National Institutes of Health (NIH) describes therapeutic peptides as suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells which can be used in treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines which have been developed for the treatment of breast cancer.

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