Transcriptome Investigation and In Vitro Verification of Curcumin-Induced HO-1 as a Feature of Ferroptosis in Breast Cancer Cells

Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment. Curcumin (CUR), a well-known cancer inhibitor, significantly inhibits the viability of breast cancer cells. Through transcriptomic analysis and flow cytometry experiments, it was found that after 48 hours of treatment of breast cancer cells at its half maximal inhibitory concentration (IC50), curcumin suppressed the viability of cancer cells via induction of ferroptotic death. Use of the ferroptosis inhibitor ferrostatin-1 and the iron chelator deferoxamine rescued cell death induced by curcumin. Furthermore, in subsequent cell validation experiments, the results showed that curcumin caused marked accumulation of intracellular iron, reactive oxygen species, lipid peroxides, and malondialdehyde, while glutathione levels were significantly downregulated. These changes are all manifestations of ferroptosis. Curcumin upregulates a variety of ferroptosis target genes related to redox regulation, especially heme oxygenase-1 (HO-1). Using the specific inhibitor zinc protoporphyrin 9 (ZnPP) to confirm the above experimental results showed that compared to the curcumin treatment group, treatment with ZnPP not only significantly improved cell viability but also reduced the accumulation of intracellular iron ions and other ferroptosis-related phenomena. Therefore, these data demonstrate that curcumin triggers the molecular and cytological characteristics of ferroptosis in breast cancer cells, and HO-1 promotes curcumin-induced ferroptosis.

Download Full-text

Triclabendazole Induces Pyroptosis by Activating Caspase-3 to Cleave GSDME in Breast Cancer Cells

Frontiers in Pharmacology ◽

10.3389/fphar.2021.670081 ◽

2021 ◽

Vol 12 ◽

Author(s):

Liang Yan ◽

Yi Liu ◽

Xue-feng Ma ◽

Dan Hou ◽

Yu-hui Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Caspase 3 ◽

Xenograft Model ◽

Specific Inhibitor ◽

Apoptotic Pathway ◽

Mitochondrial Apoptotic Pathway ◽

Protein Levels

Pyroptosis is a form of programmed cell death, in which gasdermin E (GSDME) plays an important role in cancer cells, which can be induced by activated caspase-3 on apoptotic stimulation. Triclabendazole is a new type of imidazole in fluke resistance and has been approved by the FDA for the treatment of fascioliasis and its functions partially acting through apoptosis-related mechanisms. However, it remains unclear whether triclabendazole has obvious anti-cancer effects on breast cancer cells. In this study, to test the function of triclabendazole on breast cancer, we treated breast cancer cells with triclabendazole and found that triclabendazole induced lytic cell death in MCF-7 and MDA-MB-231, and the dying cells became swollen with evident large bubbles, a typical sign of pyroptosis. Triclabendazole activates apoptosis by regulating the apoptoic protein levels including Bax, Bcl-2, and enhanced cleavage of caspase-8/9/3/7 and PARP. In addition, enhanced cleavage of GSDME was also observed, which indicates the secondary necrosis/pyroptosis is further induced by active caspase-3. Consistent with this, triclabendazole-induced GSDME–N-terminal fragment cleavage and pyroptosis were reduced by caspase-3–specific inhibitor (Ac-DEVD-CHO) treatment. Moreover, triclabendazole induced reactive oxygen species (ROS) elevation and increased JNK phosphorylation and lytic cell death, which could be rescued by the ROS scavenger (NAC), suggesting that triclabendazole-induced GSDME-dependent pyroptosis is related to the ROS/JNK/Bax-mitochondrial apoptotic pathway. Besides, we showed that triclabendazole significantly reduced the tumor volume by promoting the cleavage of caspase-3, PARP, and GSDME in the xenograft model. Altogether, our results revealed that triclabendazole induces GSDME-dependent pyroptosis by caspase-3 activation at least partly through augmenting the ROS/JNK/Bax-mitochondrial apoptotic pathway, providing insights into this on-the-market drug in its potential new application in cancer treatment.

Download Full-text

Mechanism of Growth Factor Attenuation of Cell Death in Chemotherapy Treated Breast Cancer Cells

10.21236/ada391062 ◽

2000 ◽

Author(s):

Carla Van Den Berg

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Growth Factor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Treated Breast ◽

Mechanism Of Growth ◽

Treated Breast Cancer

Download Full-text

Oxyresveratrol drives caspase-independent apoptosis-like cell death in MDA-MB-231 breast cancer cells through the induction of ROS

Biochemical Pharmacology ◽

10.1016/j.bcp.2019.113724 ◽

2020 ◽

Vol 173 ◽

pp. 113724 ◽

Cited By ~ 4

Author(s):

Damu Sunilkumar ◽

G. Drishya ◽

Aneesh Chandrasekharan ◽

Sanu K. Shaji ◽

Chinchu Bose ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells

Download Full-text

Arginine Methyltransferase PRMT1 Regulates p53 Activity in Breast Cancer

Life ◽

10.3390/life11080789 ◽

2021 ◽

Vol 11 (8) ◽

pp. 789

Author(s):

Li-Ming Liu ◽

Qiang Tang ◽

Xin Hu ◽

Jing-Jing Zhao ◽

Yuan Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Asymmetric Dimethylarginine ◽

Human Cancer ◽

Specific Inhibitor ◽

Dependent Manner ◽

Breast Tumorigenesis ◽

Stress Signals

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.

Download Full-text

Laser nanobubbles induce immunogenic cell death in breast cancer

Nanoscale ◽

10.1039/d0nr06587k ◽

2021 ◽

Vol 13 (6) ◽

pp. 3644-3653

Author(s):

Hieu T. M. Nguyen ◽

Nitesh Katta ◽

Jessica A. Widman ◽

Eri Takematsu ◽

Xu Feng ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Dendritic Cell ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cell Activation ◽

Immunogenic Cell Death ◽

Dendritic Cell Activation

Laser nanobubbles induce dendritic cell activation in breast cancer cells.

Download Full-text

Identification of Two Novel Thiophene Analogues as Inducers of Autophagy Mediated Cell Death in Breast Cancer Cells

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2021.116112 ◽

2021 ◽

pp. 116112

Author(s):

Chandrima Gain ◽

Aparna Sarkar ◽

Shrea Bural ◽

Moumita Rakshit ◽

Jeet Banerjee ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells

Download Full-text

A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03363-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiraporn Kantapan ◽

Siwaphon Paksee ◽

Aphidet Duangya ◽

Padchanee Sangthong ◽

Sittiruk Roytrakul ◽

...

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Breast Cancer Cell Lines ◽

Mesenchymal Transition ◽

Mammosphere Formation ◽

Radiation Induced

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

Download Full-text