scholarly journals A Shortage of FTH Induces ROS and Sensitizes RAS-Proficient Neuroblastoma N2A Cells to Ferroptosis

2021 ◽  
Vol 22 (16) ◽  
pp. 8898
Author(s):  
Ruiqing Lu ◽  
Yinan Jiang ◽  
Xianxin Lai ◽  
Shujie Liu ◽  
Litao Sun ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Ectopic Expression ◽  
Neural Cells ◽  
N2a Cells ◽  
Primary Mouse ◽  
Anti Cancer ◽  
Dependent Form ◽  
Almost All

Ferroptosis, an iron-dependent form of programmed cell death, has excellent potential as an anti-cancer therapeutic strategy in different types of tumors, especially in RAS-mutated ones. However, the function of ferroptosis for inhibiting neuroblastoma, a common child malignant tumor with minimal treatment, is unclear. This study investigated the anti-cancer function of ferroptosis inducer Erastin or RSL3 in neuroblastoma N2A cells. Our results show that Erastin or RSL3 induces ROS level and cell death and, therefore, reduces the viability of RAS-proficient N2A cells. Importantly, inhibitors to ferroptosis, but not apoptosis, ameliorate the high ROS level and viability defect in Erastin- or RSL3-treated cells. In addition, our data also show that N2A cells are much more sensitive to ferroptosis inducers than primary mouse cortical neural stem cells (NSCs) or neurons. Moreover, a higher level of ROS and PARylation is evidenced in N2A, but not NSCs. Mechanically, ferritin heavy chain 1 (Fth), the ferroxidase function to oxidate redox-active Fe2+ to redox-inactive Fe3+, is likely responsible for the hypersensitivity of N2A to ferroptosis induction since its expression is lower in N2A compared to NSCs; ectopic expression of Fth reduces ROS levels and cell death, and induces expression of GPX4 and cell viability in N2A cells. Most importantly, neuroblastoma cell lines express a significantly low level of Fth than almost all other types of cancer cell lines. All these data suggest that Erastin or RSL3 induce ferroptosis cell death in neuroblastoma N2A cells, but not normal neural cells, regardless of RAS mutations, due to inadequate FTH. This study, therefore, provides new evidence that ferroptosis could be a promising therapeutic target for neuroblastoma.

scholarly journals Selective Anti-Cancer Effects of Plasma-Activated Medium and Its High Efficacy with Cisplatin on Hepatocellular Carcinoma with Cancer Stem Cell Characteristics

2021 ◽  
Vol 22 (8) ◽  
pp. 3956
Author(s):  
Yan Li ◽  
Tianyu Tang ◽  
Hae June Lee ◽  
Kiwon Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Cell Lines ◽  
Primary Liver Cancer ◽  
Atmospheric Pressure Plasma ◽  
Normal Liver ◽  
Normal Liver Cell ◽  
Ample Evidence ◽  
Huh7 Cells ◽  
Anti Cancer

Hepatocellular carcinoma (HCC) is a major histological subtype of primary liver cancer. Ample evidence suggests that the pathological properties of HCC originate from hepatic cancer stem cells (CSCs), which are responsible for carcinogenesis, recurrence, and drug resistance. Cold atmospheric-pressure plasma (CAP) and plasma-activated medium (PAM) induce apoptosis in cancer cells and represent novel and powerful anti-cancer agents. This study aimed to determine the anti-cancer effect of CAP and PAM in HCC cell lines with CSC characteristics. We showed that the air-based CAP and PAM selectively induced cell death in Hep3B and Huh7 cells with CSC characteristics, but not in the normal liver cell line, MIHA. We observed both caspase-dependent and -independent cell death in the PAM-treated HCC cell lines. Moreover, we determined whether combinatorial PAM therapy with various anti-cancer agents have an additive effect on cell death in Huh7. We found that PAM highly increased the efficacy of the chemotherapeutic agent, cisplatin, while enhanced the anti-cancer effect of doxorubicin and the targeted-therapy drugs, trametinib and sorafenib to a lesser extent. These findings support the application of CAP and PAM as anti-cancer agents to induce selective cell death in cancers containing CSCs, suggesting that the combinatorial use of PAM and some specific anti-cancer agents is complemented mechanistically.

Distinct Apoptotic Responses Imparted by c-myc and max

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 1003-1010 ◽  
Author(s):  
Chadd E. Nesbit ◽  
Saijun Fan ◽  
Hong Zhang ◽  
Edward V. Prochownik
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Ectopic Expression ◽  
Drug Induced ◽  
Enhanced Sensitivity ◽  
Contrast Enhanced ◽  
Apoptotic Pathways ◽  
American Society ◽  
Induced Apoptosis ◽  
Cytokine Deprivation

Abstract The c-myc oncoprotein accelerates programmed cell death (apoptosis) after growth factor deprivation or pharmacological insult in many cell lines. We have shown that max, the obligate c-myc heterodimeric partner protein, also promotes apoptosis after serum withdrawal in NIH3T3 fibroblasts or cytokine deprivation in interleukin-3 (IL-3)-dependent 32D murine myeloid cells. We now show that c-myc– and max-overexpressing 32D cells differ in the nature of their apoptotic responses after IL-3 removal or treatment with chemotherapeutic compounds. In the presence of IL-3, c-myc overexpression enhances the sensitivity of 32D cells to Etoposide (Sigma, St Louis, MO), Adriamycin (Pharmacia, Columbus, OH), and Camptothecin (Sigma), whereas max overexpression increases sensitivity only to Camptothecin. Drug treatment of c-myc–overexpressing cells in the absence of IL-3 did not alter the spectrum of drug sensitivity other than to additively accelerate cell death. In contrast, enhanced sensitivity to Adriamycin, Etoposide, and Taxol (Bristol-Meyers Squibb, Princeton, NJ) was revealed in max-overexpressing cells concurrently deprived of IL-3. Differential rates of apoptosis were not strictly correlated with the ability of the drugs to promote G1 or G2/M arrest. Ectopic expression of Bcl-2 or Bcl-XL blocked drug-induced apoptosis in both cell lines. In contrast, whereas Bcl-2 blocked apoptosis in both cell lines in response to IL-3 withdrawal, Bcl-XL blocked apoptosis in max-overexpressing cells but not in c-myc–overexpressing cells. These results provide mechanistic underpinnings for the idea that c-myc and max modulate distinct apoptotic pathways. © 1998 by The American Society of Hematology.

scholarly journals The Comprehensive Roles of ATRANORIN, A Secondary Metabolite from the Antarctic Lichen Stereocaulon caespitosum, in HCC Tumorigenesis

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1414 ◽  
Author(s):  
Young-Jun Jeon ◽  
Sanghee Kim ◽  
Ji Hee Kim ◽  
Ui Joung Youn ◽  
Sung-Suk Suh
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Genetic Diseases ◽  
Annexin V ◽  
Cancer Therapeutics ◽  
Metastatic Potential ◽  
Anti Cancer ◽  
Experimental Approaches ◽  
The Antarctic ◽  
Death Determination

Hepatocellular carcinoma (HCC) is one of the most deadly genetic diseases, but surprisingly chemotherapeutic approaches against HCC are only limited to a few targets. In particular, considering the difficulty of a chemotherapeutic drug development in terms of cost and time enforces searching for surrogates to minimize effort and maximize efficiency in anti-cancer therapy. In spite of the report that approximately one thousand lichen-derived metabolites have been isolated, the knowledge about their functions and consequences in cancer development is relatively limited. Moreover, one of the major second metabolites from lichens, Atranorin has never been studied in HCC. Regarding this, we comprehensively analyze the effect of Atranorin by employing representative HCC cell lines and experimental approaches. Cell proliferation and cell cycle analysis using the compound consistently show the inhibitory effects of Atranorin. Moreover, cell death determination using Annexin-V and (Propidium Iodide) PI staining suggests that it induces cell death through necrosis. Lastly, the metastatic potential of HCC cell lines is significantly inhibited by the drug. Taken these together, we claim a novel functional finding that Atranorin comprehensively suppresses HCC tumorigenesis and metastatic potential, which could provide an important basis for anti-cancer therapeutics.

scholarly journals Anti-Cancer Effect of Kaffir Lime (Citrus Hystrix DC) Leaf Extract in Cervical Cancer and Neuroblastoma Cell Lines

2015 ◽  
Vol 14 ◽  
pp. 465-468 ◽  
Author(s):  
Woro Anindito Sri Tunjung ◽  
Jindrich Cinatl ◽  
Martin Michaelis ◽  
C. Mark Smales
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Leaf Extract ◽  
Neuroblastoma Cell ◽  
Anti Cancer ◽  
Neuroblastoma Cell Lines

scholarly journals The HDAC6/8/10 inhibitor TH34 induces DNA damage-mediated cell death in human high-grade neuroblastoma cell lines

2018 ◽  
Vol 92 (8) ◽  
pp. 2649-2664 ◽  
Author(s):  
Fiona R. Kolbinger ◽  
Emily Koeneke ◽  
Johannes Ridinger ◽  
Tino Heimburg ◽  
Michael Müller ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
High Grade ◽  
Neuroblastoma Cell Lines

Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines

2012 ◽  
Vol 28 (4) ◽  
pp. 201-212 ◽  
Author(s):  
Eystein Oveland ◽  
Line Wergeland ◽  
Randi Hovland ◽  
James B. Lorens ◽  
Bjørn Tore Gjertsen ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Ectopic Expression ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

scholarly journals Cell Death Induction Potential in Seed Extracts- Hidden and Bioactive Phytochemical Treasures

2021 ◽  
Vol 20 (4) ◽  
Author(s):  
R. Rajasekaran ◽  
P. K. Suresh
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Grape Seed ◽  
Seed Extract ◽  
Chemotherapeutic Drugs ◽  
Bioactive Components ◽  
Induce Cell Death ◽  
Grape Seed Proanthocyanidins ◽  
Anti Cancer ◽  
Seed Extracts

Seeds have been known to possess bioactive components with anti-cancer properties. This study aims to demonstrate the processes by which seed extracts from various sources induce cell death. Several assays have been employed to demonstrate the induction of cell death by the respective seed extracts. This review also underscores the importance of Grape Seed Proanthocyanidins (GSPs) in terms of inducing the aforesaid physiological form of seed extract-induced cell death. Furthermore, this review highlights the critical and pressing need to conduct comparative HTS-based strategies (with a battery of cell lines representing different cancers) to identify the major seed extracts that can reproducibly serve to augment the cell death induction capabilities of the existing battery of chemotherapeutic drugs/natural alternatives.

The In Vitro Anti-Cancer Activities of 17βH-Neriifolin Isolated from Cerbera odollam and its Binding Activity on Na+, K+-ATPase

2020 ◽  
Vol 21 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Nurhanan M. Yunos ◽  
Asiah Osman ◽  
Muhammad H. Jauri ◽  
Nor J. Sallehudin ◽  
Siti Syarifah Mohd Mutalip
Keyword(s):  
Cell Death ◽  
Binding Energy ◽  
Cell Lines ◽  
Malachite Green ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Α Subunit ◽  
Anti Cancer ◽  
Malachite Green Assay

Background: 17βH-neriifolin, a cardiac glycoside compound had been successfully isolated from Cerbera odollam leaves based on the bioassay guided-isolation procedure. The aim of these studies were to determine the in vitro anti-cancer and binding effects of 17βH-neriifolin on Na+, K+-ATPase. Methods: The in vitro anti-cancer effects were evaluated using Sulphorhodamine B and Hoescht 33342 assays. The Na+, K+-ATPase assay was carried out using Malachite Green assay. In silico molecular docking studies and in vitro malachite green assay were used to predict the binding activities of 17βH-neriifolin on Na+, K+-ATPase and ouabain was also included as for comparison studies. Results: The compound was tested against breast (MCF-7, T47D), colorectal (HT-29), ovarian (A2780, SKOV-3) and skin (A375) cancer cell lines that gave IC50 values ranged from 0.022 ± 0.0015 to 0.030 ± 0.0018 μM. The mechanism of cell death of 17βH-neriifolin was further evaluated using Hoescht 33342 assay and it was found that the compound killed the cancer cells via apoptosis. 17βHneriifolin and ouabain both bound at α-subunit in Na+, K+-ATPase and their binding energy were - 8.16 ± 0.74 kcal/mol and -8.18 ± 0.48 kcal/mol respectively. Conclusion: The results had confirmed the anti-proliferative effects exerted by 17βH-neriifolin in the breast, colorectal, ovarian and skin cancer cell lines. 17βH-neriifolin had shown to cause apoptotic cell death in the respective cancer cell lines.17βH-neriifolin and ouabain both bound at α-subunit in Na+, K+-ATPase and their binding energy were -8.16 ± 0.74 kcal/mol and -8.18 ± 0.48 kcal/mol respectively. This is the first report to reveal that 17βH-neriifolin managed to bind to the pocket of α-subunit of Na+.K+-ATPase.

The role of c-Met inhibition for neuroblastoma treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10041-10041
Author(s):  
Peter Zage ◽  
Kathy Scorsone ◽  
Linna Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuroblastoma Tumor ◽  
Met Phosphorylation

10041 Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood. Many children present with high-risk disease characterized by rapid tumor growth, resistance to chemotherapy, and widespread metastasis, and novel therapies are needed. Previous studies have identified a role for the HGF/c-Met pathway in the pathogenesis of neuroblastoma. We hypothesized that EMD1214063 would be effective against neuroblastoma tumor cells and tumors in preclinical models via inhibition of HGF/c-Met signaling. Methods: We determined the expression of c-Met in a panel of neuroblastoma tumor cells and neuroblastoma cell viability after treatment with EMD1214063 using MTT assays. Analyses were performed for changes in cell morphology, cell cycle progression, and cell death via apoptosis after EMD1214063 treatment. To investigate the efficacy of EMD1214063 against neuroblastoma tumors in vivo, neuroblastoma cells were injected orthotopically into immunocompromised mice, and the mice in which tumors developed were treated with oral EMD1214063. Results: All neuroblastoma cell lines were sensitive to EMD1214063, and IC50 values ranged from 2.4 - 8.5 mcM. EMD1214063 treatment inhibited HGF-mediated c-Met phosphorylation in neuroblastoma cells. EMD1214063 induced cell cycle arrest in neuroblastoma tumor cells with high c-Met expression, and induced apoptosis in all tested cell lines. In mice with neuroblastoma xenograft tumors, EMD1214063 inhibited tumor growth. Conclusions: Treatment of neuroblastoma tumor cells with EMD1214063 inhibits HGF-induced c-Met phosphorylation and results in cell death. Furthermore, EMD1214063 induces cell cycle arrrest prior to cell death in neuroblastoma tumor cells with high c-Met expression. EMD1214063 treatment is effective in reducing tumor growth in vivo in mice. Inhibition of c-Met represents a potential new therapeutic strategy for neuroblastoma, and further preclinical studies of EMD1214063 are warranted.

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