DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death

AbstractDrug resistance is a major obstacle to the treatment of most human tumors. In this study, we find that dual-specificity phosphatase 16 (DUSP16) regulates resistance to chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant to chemotherapy-induced cell death than cells with lower DUSP16 expression. Overexpression of DUSP16 in cancer cells leads to increased resistance to cell death upon chemotherapy treatment. In contrast, knockdown of DUSP16 in cancer cells increases their sensitivity to treatment. Mechanistically, DUSP16 inhibits JNK and p38 activation, thereby reducing BAX accumulation in mitochondria to reduce apoptosis. Analysis of patient survival in head & neck cancer and breast cancer patient cohorts supports DUSP16 as a marker for sensitivity to chemotherapy and therapeutic outcome. This study therefore identifies DUSP16 as a prognostic marker for the efficacy of chemotherapy, and as a therapeutic target for overcoming chemoresistance in cancer.

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Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.763500 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yaru Li ◽

Yilong Zhu ◽

Jicheng Han ◽

Jinbo Fang ◽

Zhiru Xiu ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Tumor Cell Death ◽

Induce Cell Death ◽

Chemotherapy Drugs ◽

Signaling Axis ◽

Mcf 7

Ad-VT (Ad-Apoptin-hTERTp-E1a) is a type of oncolytic adenovirus with dual specific tumor cell death ability. It can effectively induce cell death of breast cancer cells and has better effect when used in combination with chemotherapy drugs. However, it has not been reported whether Ad-VT reduces the resistance of breast cancer cells to chemotherapy drugs. The purpose of this study is to investigate the effect of Ad-VT on drug resistance of Adriamycin-resistant breast cancer cells. For this, the effects of different doses of Ad-VT on the resistance of breast cancer cells to Adriamycin were analyzed using qualitative and quantitative experiments in vitro and in vivo. The Ad-VT can reduce the resistance of MCF-7/ADR to adriamycin, which is caused by the reduction of MRP1 protein level in MCF-7/ADR cells after treatment with Ad-VT, and MRP1 can be interfered with by autophagy inhibitors. Subsequently, the upstream signal of autophagy was analyzed and it was found that Ad-VT reduced the resistance of cells to doxorubicin by reducing the level of mTOR, and then the analysis of the upstream and downstream proteins of mTOR found that Ad-VT increased the sensitivity of MCF-7/ADR cells to adriamycin by activating AMPK-mTOR-eIF4F signaling axis. Ad-VT can not only significantly induce cell death in MCF-7/ADR cells, but also improved their sensitivity to Adriamycin. Therefore, the combination of Ad-VT and chemotherapy drugs may become a new strategy for the treatment of breast cancer in overcoming Adriamycin resistance.

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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

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ent-Kaurane Diterpenoids from Croton tonkinensis Induce Apoptosis in Colorectal Cancer Cells through the Phosphorylation of JNK Mediated by Reactive Oxygen Species and Dual-Specificity JNK Kinase MKK4

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520614666140127111407 ◽

2014 ◽

Vol 14 (7) ◽

pp. 1051-1061 ◽

Cited By ~ 8

Author(s):

Phuong Thuong ◽

Nguyen Khoi ◽

Saho Ohta ◽

Shinichiro Shiota ◽

Hironori Kanta ◽

...

Keyword(s):

Colorectal Cancer ◽

Reactive Oxygen Species ◽

Cancer Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Dual Specificity ◽

Colorectal Cancer Cells

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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

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Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Molecules ◽

10.3390/molecules26051261 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1261

Author(s):

Nurul Fattin Che Rahim ◽

Yazmin Hussin ◽

Muhammad Nazirul Mubin Aziz ◽

Nurul Elyani Mohamad ◽

Swee Keong Yeap ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Death ◽

Cancer Cells ◽

Cell Lines ◽

Curcuma Longa ◽

Metastatic Colon Cancer ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Sw620 Cell

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.

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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.

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Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance

Cancers ◽

10.3390/cancers13081792 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1792

Author(s):

Debashri Manna ◽

Devanand Sarkar

Keyword(s):

Drug Resistance ◽

Cancer Cells ◽

Cancer Development ◽

Epigenetic Alterations ◽

Hallmarks Of Cancer ◽

Comprehensive Description ◽

Molecular Abnormalities ◽

Selective Pressures ◽

Resistance To Chemotherapy

Cancer development results from the acquisition of numerous genetic and epigenetic alterations in cancer cells themselves, as well as continuous changes in their microenvironment. The plasticity of cancer cells allows them to continuously adapt to selective pressures brought forth by exogenous environmental stresses, the internal milieu of the tumor and cancer treatment itself. Resistance to treatment, either inherent or acquired after the commencement of treatment, is a major obstacle an oncologist confronts in an endeavor to efficiently manage the disease. Resistance to chemotherapy, chemoresistance, is an important hallmark of aggressive cancers, and driver oncogene-induced signaling pathways and molecular abnormalities create the platform for chemoresistance. The oncogene Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) is overexpressed in a diverse array of cancers, and its overexpression promotes all the hallmarks of cancer, such as proliferation, invasion, metastasis, angiogenesis and chemoresistance. The present review provides a comprehensive description of the molecular mechanism by which AEG-1 promotes tumorigenesis, with a special emphasis on its ability to regulate chemoresistance.

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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

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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.

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