scholarly journals Roles of ferroptosis in urologic malignancies

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shankun Zhao ◽  
Peng Li ◽  
Weizhou Wu ◽  
Qinzhang Wang ◽  
Biao Qian ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Positive Association ◽  
Therapeutic Effects ◽  
Urologic Oncology ◽  
Dependent Form ◽  
Per Se ◽  
Urologic Malignancies ◽  
Urologic Cancers ◽  
Anticancer Response ◽  
Therapeutic Responses

AbstractFerroptosis, an iron-dependent form of non-apoptotic cell death, is believed to strongly contribute to the pathogenesis of multiple cancers. Recently, the positive association between ferroptosis and urologic malignancies has drawn considerable attention, while a comprehensive review focused on this issue is absent. Based on this review, ferroptosis has been implicated in the development and therapeutic responses of prostate cancer, kidney cancer, and bladder cancer. Mechanistically, a large number of biomolecules and tumor-associated signaling pathways, including DECR1, PANX2, HSPB1, ACOT8, SUV39H1, NCOA4, PI3K-AKT-mTOR signaling, VHL/HIF-2α pathway, and Hippo/TAZ signaling pathway, have been reported to regulate ferroptosis in urologic cancers. Ferroptosis inducers, such as erastin, ART, CPNPs, and quinazolinyl-arylurea derivatives, exert potential therapeutic effects per se and/or enhance the anticancer response of other anticancer drugs in urologic oncology. A better understanding of ferroptosis may provide a promising way to treat therapy-resistant urologic cancers.

Quercetin in attenuation of ischemic/reperfusion injury: A review

2020 ◽  
Vol 13 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Saeed Samarghandian ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
Md Shahinozzaman ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Blood Supply ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Membrane Integrity ◽  
Therapeutic Effects ◽  
Molecular Pathways ◽  
Cell Membrane Integrity ◽  
Cell Membrane Disruption

Background: Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply increases, but it deteriorates condition, and leads to generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-B, PI3K/Akt and so on. Methods: In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-B, MAPK and so on. Results and conclusion: Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via down-regulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for delivery of quercetin, enhancing its bioavailability and efficacy in alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.

scholarly journals The therapeutic effects of Physalis alkekengi hydroalcoholic extract on estrogen receptor-positive breast cancer mice model: possible role of autophagy in this therapeutic response

2020 ◽  
Vol 22 (4) ◽  
pp. 181-186
Author(s):  
Zahra Zare ◽  
Maryam Teimouri
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Body Weight ◽  
Apoptotic Cell ◽  
Breast Tumors ◽  
Effective Dosage ◽  
Control Group ◽  
Specific Gene ◽  
Therapeutic Effects ◽  
Hydroalcoholic Extract

Background and aims: Although some preclinical and clinical studies have extensively confirmed the pharmacological effects of the hydroalcoholic extract (HE) of Physalis alkekengi on several diseases, little is known about the effects of P. alkekengi HE (PAHE) on breast cancer. Therefore, this study aimed to investigate the therapeutic effect of PAHE on estrogen receptor+ breast cancer. Methods: To this end, tumors were created in mice by injecting MC4L2 cells into the sternum of the mice. Then, the animals were gavaged for 16 days at 10, 50, and 100 mg/kg daily of PAHE. In addition, the tumor growth and body weight of the mice were measured on the 16th day, and they were killed on 21st day. Finally, their tumor tissues were removed and the apoptotic cell tissue and expression of the ATG-5 gene were studied as well. The experiments were repeated three times, and the data were analyzed using SPSS software (P<0.001 and P<0.05). Results: The average body weight of the control group significantly decreased 16 days after tumor establishment (P<0.001). Further, the PAHE inhibited the growth of the breast cancer tumor in higher doses (50 & 100 mg/kg, P<0.001). Based on the results, a significant histopathological alteration was found in the breast tumors of the PAHE-treated groups compared with the control group, including the decreased level of mitotic cells the intensive level of necrotic cells and lymphocyte infiltration into the breast tumors bearing mice 21 days after PAHE administration (P=0.012). Eventually, PAHE significantly increased the mRNA level of the expression of the autophagy ATG-5 specific gene in the effective dosage-treated group (50 mg/kg, P=0.037). Conclusion: The evidence suggests that the PAHE has a suitable efficacy for the treatment of ER+ breast cancer by promoting autophagy mechanisms into these tumor types

scholarly journals The Vitamin E Derivative Gamma Tocotrienol Promotes Anti-Tumor Effects in Acute Myeloid Leukemia Cell Lines

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2808 ◽  
Author(s):  
Ghanem ◽  
Zouein ◽  
Mohamad ◽  
Hodroj ◽  
Haykal ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Vitamin E ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Apoptotic Cell ◽  
Leukemia Cell ◽  
Therapeutic Effects ◽  
Apoptotic Pathway ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a blood cancer characterized by the formation of faulty defective myelogenous cells with morphological heterogeneity and cytogenic aberrations leading to a loss of their function. In an attempt to find an effective and safe AML treatment, vitamin E derivatives, including tocopherols were considered as potential anti-tumor compounds. Recently, other isoforms of vitamin E, namely tocotrienols have been proposed as potential potent anti-cancerous agents, displaying promising therapeutic effects in different cancer types. In this study we evaluated the anti-cancerous effects of γ-tocotrienol, on AML cell lines in vitro. For this purpose, AML cell lines incubated with γ-tocotrienol were examined for their viability, cell cycle status, apoptotic cell death, DNA fragmentation, production of reactive oxygen species and expression of proapoptotic proteins. Our results showed that γ-tocotrienol exhibits time and dose-dependent anti-proliferative, pro-apoptotic and antioxidant effects on U937 and KG-1 cell lines, through the upregulation of proteins involved in the intrinsic apoptotic pathway.

Antisense to the Epstein-Barr Virus (EBV)-Encoded Latent Membrane Protein 1 (LMP-1) Suppresses LMP-1 and Bcl-2 Expression and Promotes Apoptosis in EBV-Immortalized B Cells

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1721-1727 ◽  
Author(s):  
Jamie L. Kenney ◽  
Mary E. Guinness ◽  
Tyler Curiel ◽  
Jill Lacy
Keyword(s):  
Membrane Protein ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Antitumor Agents ◽  
Apoptotic Cell ◽  
Latent Membrane Protein ◽  
Therapeutic Effects ◽  
Inhibition Of Proliferation ◽  
Barr Virus ◽  
Epstein Barr

Abstract The Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP-1) is required for viral transformation and functions to protect cells from apoptotic cell death, in part, by induction of antiapoptotic genes, including Bcl-2 and A20. We have used antisense oligodeoxynucleotides targeted to LMP-1 as a strategy to suppress LMP-1 expression and thereby inhibit its functions. We have shown that levels of LMP-1 protein in EBV-positive lymphoblastoid cell lines can be reduced by in vitro treatment with unmodified oligodeoxynucleotides targeted to the first five codons of the LMP-1 open-reading frame. Furthermore, suppression of LMP-1 was associated with molecular and phenotypic effects that included downregulation of the LMP-1–inducible antiapoptotic genes, Bcl-2 and Mcl-1, inhibition of proliferation, stimulation of apoptosis, and enhancement of sensitivity to the chemotherapeutic agent, etoposide. These effects were largely sequence-specific and observed in EBV-positive, but not EBV-negative cell lines. These studies suggest that lowering expression of LMP-1 in EBV-associated malignancy might have therapeutic effects and might synergize with other antitumor agents. © 1998 by The American Society of Hematology.

scholarly journals Comparative Therapeutic Effects of Minocycline Treatment and Bone Marrow Mononuclear Cell Transplantation following Striatal Stroke

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Celice C. Souza ◽  
Michelle Castro da Silva ◽  
Rosana Telma Lopes ◽  
Marcelo M. Cardoso ◽  
Lucas Lacerda de Souza ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Cresyl Violet ◽  
Bone Marrow Mononuclear Cell ◽  
Histopathological Analysis ◽  
Therapeutic Effects ◽  
Apoptotic Cells ◽  
Therapeutic Approaches ◽  
Adult Rats ◽  
Minocycline Treatment ◽  
Active Caspase

We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated (N=5), minocycline-treated (N=5), and BMMC-transplanted (N=5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia. Animals were perfused at 7 days after ischemic induction. Coronal sections were stained with cresyl violet for gross histopathological analysis and immunolabeled for the identification of neuronal bodies (NeuN), activated microglia/macrophages (ED1), and apoptotic cells (active caspase-3). BMMC transplantation and minocycline reduced the number of ED1+ cells (p<0.05, ANOVA-Tukey), but BMMC afforded better results. Both treatments afforded comparable levels of neuronal preservation compared to control (p>0.05). BMMC transplantation induced a higher decrease in the number of apoptotic cells compared to control and minocycline treatment. Both therapeutic approaches improved functional recovery in ischemic animals. The results suggest that BMMC transplantation is more effective in modulating microglial activation and reducing apoptotic cell death than minocycline, although both treatments are equally efficacious on improving neuronal preservation.

scholarly journals The Role of Mitochondria in Pyroptosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Qian Li ◽  
Nengxian Shi ◽  
Chen Cai ◽  
Mingming Zhang ◽  
Jing He ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Pathological Process ◽  
Mitochondrial Outer Membrane ◽  
Therapeutic Effects ◽  
Mitochondrial Outer Membrane Permeabilization ◽  
Regulated Cell Death ◽  
Clinical Benefits ◽  
Regulate Cell Death

Pyroptosis is a recently discovered aspartic aspart-specific cysteine protease (Caspase-1/4/5/11) dependent mode of gene-regulated cell death cell death, which is represented by the rupture of cell membrane perforations and the production of proinflammatory mediaters like interleukin-18(IL-18) and interleukin-1β (IL-1β). Mitochondria also play an important role in apoptotic cell death. When it comes to apoptosis of mitochondrion, mitochondrial outer membrane permeabilization (MOMP) is commonly known to cause cell death. As a downstream pathological process of apoptotic signaling, MOMP participates in the leakage of cytochrome-c from mitochondrion to the cytosol and subsequently activate caspase proteases. Hence, targeting MOMP for the sake of manipulating cell death presents potential therapeutic effects among various types of diseases, such as autoimmune disorders, neurodegenerative diseases, and cancer. In this review, we highlights the roles and significance of mitochondria in pyroptosis to provide unexplored strategies that target the mitochondria to regulate cell death for clinical benefits.

scholarly journals Common and dissociable contributions of alexithymia and autism to domain-specific interoceptive dysregulations – a dimensional neuroimaging approach

2018 ◽  
Author(s):  
Jialin Li ◽  
Lei Xu ◽  
Xiaoxiao Zheng ◽  
Meina Fu ◽  
Feng Zhou ◽  
...  
Keyword(s):  
Positive Association ◽  
Autism Spectrum ◽  
Physical Pain ◽  
Domain Specific ◽  
Fmri Study ◽  
Empathy Deficits ◽  
Affective Pain ◽  
Per Se ◽  
Neural Reactivity ◽  
The Impact

AbstractAlexithymia represents a transdiagnostic marker across psychiatric entities associated with emotional impairments, including autism spectrum disorders (ASD). Accumulating evidence suggests that interoceptive dysfunctions that underpin the core symptomatic emotion recognition and empathy deficits in ASD may be contributed to by high levels of alexithymia rather than autistic symptoms per se. However, previous findings are hampered by generally elevated alexithymia in ASD patients, and thus were not able to differentiate common and distinct contributions across the entire spectrum of variations of autism and alexithymia. Moreover, the multi-factorial nature of the domains affected, such as distinct neural reactivity towards perceiving physical and affective pain, has not been accounted for. Against this background the present fMRI study employed a dimensional trait approach in n = 242 healthy subjects to determine common and distinct associations between both traits and pain empathic responses towards physical and affective pain. Higher levels of alexithymia associated with increased left anterior insula pain empathic reactivity. Disentangling these effects revealed a positive association during perceived physical pain, but a negative one during affective pain. No significant associations with trait autism were found, but an interaction effect between the trait dimensions was observed in the mid-cingulate cortex. Moderation analysis demonstrated that trait autism only impacted mid-cingulate reactivity towards physical pain in high alexithymia subjects, whereas reactivity towards affective pain was specifically associated with trait autism in low alexithymia subjects. Findings confirm previous patient studies suggesting that alexithymia rather than autism per se may drive altered insula pain empathic reactivity. Importantly, the present approach allowed for the first time to demonstrate that the impact of alexithymia on insula reactivity varies as a function of the pain empathic domain and that effects on other core empathy nodes evolve in interaction with trait autism.

scholarly journals CD44s Induces miR-629-3p Expression in Association with Cisplatin Resistance in Head and Neck Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 856
Author(s):  
Junichiro Chikuda ◽  
Kurataka Otsuka ◽  
Iwao Shimomura ◽  
Kagenori Ito ◽  
Hiroaki Miyazaki ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Target Genes ◽  
Cisplatin Resistance ◽  
Apoptotic Cell ◽  
Standard Form ◽  
Therapeutic Effects ◽  
Gene Expressions

Cisplatin (cis-diamminedichloroplatinum II [CDDP] ) is a well-known chemotherapeutic drug that has been used for the treatment of various types of human cancers, including head and neck cancer. Cisplatin exerts anticancer effects by causing DNA damage, replication defects, transcriptional inhibition, cell cycle arrest, and the induction of apoptosis. However, drug resistance is one of the most serious problems with cancer chemotherapy, and it causes expected therapeutic effects to not always be achieved. Here, we analyzed global microRNA (miRNA) expression in CD44 standard form (CD44s)-expressing SAS cells, and we identified miR-629-3p as being responsible for acquiring anticancer drug resistance in head and neck cancer. The introduction of miR-629-3p expression inhibited apoptotic cell death under cisplatin treatment conditions, and it promoted cell migration. Among the computationally predicted target genes of miR-629-3p, we found that a number of gene expressions were suppressed by the transfection with miR-629-3p. Using a xenografting model, we showed that miR-629-3p conferred cisplatin resistance to SAS cells. Clinically, increased miR-629-3p expression tended to be associated with decreased survival in head and neck cancer patients. In conclusion, our data suggest that the increased expression of miR-629-3p provides a mechanism of cisplatin resistance in head and neck cancer and may serve as a therapeutic target to reverse chemotherapy resistance.

Tepotinib inhibits the epithelial-mesenchymal transition and tumor growth of gastric cancers via increasing GSK3β, ECAD, MUC5AC, and MUC6.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16562-e16562
Author(s):  
Dae Young Zang ◽  
Sung-Hwa Sohn ◽  
Bohyun Kim ◽  
Hee Jung Sul ◽  
Jinhui Jeong ◽  
...  
Keyword(s):  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Apoptotic Cell ◽  
Xenograft Model ◽  
Control Group ◽  
Therapeutic Effects ◽  
Human Gastric Cancer ◽  
Beta Catenin ◽  
Aberrant Expression ◽  
Mesenchymal Transition

e16562 Background: Aberrant expression of mucins can promote the epithelial-mesenchymal transition (EMT), which leads to enhanced tumorigenesis. Carcinogenesis-related pathways involving c-MET and beta-catenin involve mucins. This study characterized expressions of MET, MUC5AC, MUC5B, and MUC6 EMT signaling in human gastric cancer (GC) cell lines, and further characterized the differential susceptibility of these cell lines to tepotinib. Methods: We assessed the antitumor activity of tepotinib in GC cell lines. The effect of tepotinib on cell viability (IC50), apoptotic cell death, the EMT, and c-MET and beta-catenin signaling were evaluated by MTS assay, flow cytometry, western blotting, and qRT-PCR. Antitumor efficacy was assessed in MKN45 xenograft mice. Results: Tepotinib treatment showed dose-dependent growth inhibition of c-MET-amplified SNU620, MKN45, and KATO III cells with concomitant induction of apoptosis, but tepotinib treatment did not have an effect on c-MET-reduced MKN28 and AGS cells. Tepotinib treatment also significantly reduced expressions of phospho-c-MET, total c-MET, phospho-ERK, total ERK, beta-catenin, and c-Myc protein in SNU620 and MKN45 cells. In contrast, this drug was only slightly active against KATO III cells. Notably, tepotinib significantly reduced the expressions of EMT promotion genes such as MMP7, COX-2, WNT1, MUC5B, and c-Myc in c-MET-expressed GC cells, and increased expressions of EMT suppression genes such as MUC5AC, MUC6, GSK3beta, and ECAD. In a murine xenograft model, tumor volumes were significantly reduced in the tepotinib-treated group, when administered by daily oral gavage at a dose of 10mg/kg/day. Histologically, tepotinib induced more necrosis than in the control group. Conclusions: These data show the possibility that tepotinib may have therapeutic effects in c-MET-amplified GC, suggesting that clinical studies need to confirm the therapeutic effect.

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