scholarly journals Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Olga Koval ◽  
Galina Kochneva ◽  
Anastasiya Tkachenko ◽  
Olga Troitskaya ◽  
Galina Sivolobova ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Antitumor Immunity ◽  
Cell Infection ◽  
Delay Tumor Growth ◽  
Gm Csf ◽  
Cell Death Pathways ◽  
Vaccinia Viruses ◽  
Caspase 7 ◽  
Double Recombinant

Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX. However, only VV-GMCSF-Lact efficiently decreased the mitochondrial membrane potential of infected cancer cells. Investigating immunogenic cell death markers in cancer cells infected with recombinant VVs, we demonstrated that all tested recombinant VVs were efficient in calreticulin and HSP70 externalization, decrease of cellular HMGB1, and ATP secretion. The comparison of antitumor activity against advanced MDA-MB-231 tumor revealed that both recombinants VV-GMCSF-Lact and VV-GMCSF-Apo efficiently delay tumor growth. Our results demonstrate that the composition of GM-CSF and apoptosis-inducing proteins in the VV genome is very efficient tool for specific killing of cancer cells and for activation of antitumor immunity.

scholarly journals Evaluation of cell death pathways initiated by antitumor drugs melatonin and valproic acid in bladder cancer cells

FEBS Open Bio ◽  
2017 ◽  
Vol 7 (6) ◽  
pp. 798-810 ◽  
Author(s):  
Siwei Liu ◽  
Bilin Liang ◽  
Huiting Jia ◽  
Yuhan Jiao ◽  
Zhongqiu Pang ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Bladder Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Antitumor Drugs ◽  
Cell Death Pathways ◽  
Bladder Cancer Cells

scholarly journals Oncolytic Viruses As Immunotherapeutic Agents for the Treatment of Malignant Tumors

2019 ◽  
Vol 74 (2) ◽  
pp. 108-117
Author(s):  
Alexander I. Glukhov ◽  
Dmitry A. Sivokhin ◽  
Daria A. Seryak ◽  
Tatyana S. Rodionova ◽  
Margarita I. Kamynina
Keyword(s):  
Cell Death ◽  
Antitumor Immunity ◽  
Randomized Clinical Trials ◽  
Tumor Antigens ◽  
Malignant Tumors ◽  
Oncolytic Viruses ◽  
Type I Interferons ◽  
Type I ◽  
Gm Csf ◽  
Cancer Cell Death

Oncolytic viruses (OVs) are novel and rapidly developing class of therapeutic agents for combating cancer, which can effectively infect and destroy tumor cells, leaving healthy tissues intact. Many viruses have a natural antitumor activity which causes cytolysis of cancer cells due to direct pathogenic action. Along with non-immunogenic cell death, oncolytic viruses have been shown to be capable of inducing immunogenic cancer cell death (necrosis, pyroptosis, etc.) accompanied by the release of OV-lysed tumor-associated antigens (TAAs). Releasing DAMPs and TAAs, in its turn, leads to the activation of adaptive antitumor immunity. In order to further enhance the antitumor immunity, OVs have been armed with immunostimulatory transgenes such as granulocyte-macrophage colony-stimulating factor (GM-CSF), type I interferons, interleukins (IL-2, 12, 15), costimulatory ligands (CD40, CD80), tumor antigens («prime-boost» vaccination), which further enhances the safety and effectiveness of oncolytic virotherapy. Preliminary results of randomized clinical trials of different approaches of oncolytic virotherapies in combination with immunotherapy confirm their high efficacy. However, there are some drawbacks, which necessitates their further study.

scholarly journals Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matyas Abel Tsegaye ◽  
Jianping He ◽  
Kyle McGeehan ◽  
Ireland M. Murphy ◽  
Mati Nemera ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Protein C ◽  
Tumor Tissue ◽  
Oncogenic Signaling ◽  
Inhibitory Protein ◽  
Cell Death Pathways ◽  
Apoptotic Protein ◽  
Cellular Context ◽  
Context Dependent

AbstractInhibition of programmed cell death pathways is frequently observed in cancer cells where it functions to facilitate tumor progression. However, some proteins involved in the regulation of cell death function dichotomously to both promote and inhibit cell death depending on the cellular context. As such, understanding how cell death proteins are regulated in a context-dependent fashion in cancer cells is of utmost importance. We have uncovered evidence that cellular FLICE-like Inhibitory Protein (c-FLIP), a well-known anti-apoptotic protein, is often downregulated in tumor tissue when compared to adjacent normal tissue. These data argue that c-FLIP may have activity distinct from its canonical role in antagonizing cell death. Interestingly, we have discovered that detachment from extracellular matrix (ECM) serves as a signal to elevate c-FLIP transcription and that oncogenic signaling blocks ECM-detachment-induced c-FLIP elevation. In addition, our data reveal that downregulation of c-FLIP promotes luminal filling in mammary acini and that c-FLIP overexpression in cancer cells inhibits colony formation in cells exposed to ECM-detachment. Taken together, our study reveals an unexpected, non-apoptotic role for c-FLIP during ECM-detachment and raises the possibility that c-FLIP may have context-dependent roles during tumorigenesis.

scholarly journals A Priori Activation of Apoptosis Pathways of Tumor (AAAPT) Technology: Development of Targeted Apoptosis Initiators for Cancer Treatment

2019 ◽  
Author(s):  
Raghu Pandurangi ◽  
Marco Tomasetti ◽  
Thillai Verapazham Sekar ◽  
Ramasamy Paulmurugan ◽  
Cynthia Ma ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Technology Development ◽  
Tumor Regression ◽  
A Priori ◽  
Specific Cell ◽  
Cell Death Pathways ◽  
Survival Pathways ◽  
Apoptosis Pathways

AbstractCancer cells develop tactics to circumvent the interventions by desensitizing themselves to interventions. The principle routes of desensitization include a) activation of survival pathways (e.g. NF-kB, PARP) and b) downregulation of cell death pathways (e.g. CD95/CD95L). As a result, it requires high therapeutic dose to achieve tumor regression which, in turn damages normal cells through the collateral damaging effects. Methods are needed to sensitize the low and non-responsive resistant tumor cells including cancer stem cells (CSCs) in order to evoke a better response from the current treatments. Current treatments including chemotherapy can induce cell death only in bulk cancer cells sparing CSCs and cancer resistant cells (CRCs) which are shown to be responsible for high recurrence of disease and low patient survival. Here, we report several novel tumor targeted sensitizers derived from the natural Vitamin E analogue (AMP-001-003). The drug design is based on a novel concept “A priori activation of apoptosis pathways of tumor technology (AAAPT) which is designed to activate specific cell death pathways and inhibit survival pathways simultaneously. Our results indicate that AMP-001-003 sensitize various types of cancer cells including MDA-MB-231 (triple negative breast cancer), PC3 (prostate cancer) and A543 (ling cancer) cells resulting in reducing the IC-50 of doxorubicin in vitro. At higher dose, AMP-001 acts as an anti-tumor agent on its own. The synergy between AMP-001 and doxorubicin could pave a new pathway to use AMP-001 as a neoadjuvant to chemotherapy to achieve a better efficacy and reduced off-target toxicity by the current treatments.Summary StatementA Priori Activation of Apoptosis Pathways of Tumor often referred to as “AAAPT” is a novel targeted tumor sensitizing technology which synergizes with chemotherapy to enhance the treatment efficacy.

scholarly journals Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2009 ◽  
Author(s):  
Dominique Delmas ◽  
Jianbo Xiao ◽  
Anne Vejux ◽  
Virginie Aires
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Organic Anion ◽  
Chemotherapeutic Agents ◽  
Normal Cells ◽  
Antiapoptotic Proteins ◽  
Cell Death Pathways ◽  
Anion Transporters ◽  
Atp Binding Cassettes

Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle—thus forcing them to evolve towards a process of cell death—and accumulating cancer cells in a phase of the cell cycle—thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.

scholarly journals Iron and Cancer

2018 ◽  
Vol 38 (1) ◽  
pp. 97-125 ◽  
Author(s):  
Suzy V. Torti ◽  
David H. Manz ◽  
Bibbin T. Paul ◽  
Nicole Blanchette-Farra ◽  
Frank M. Torti
Keyword(s):  
Cell Death ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Excess Iron ◽  
Cell Death Pathways ◽  
Dependent Form ◽  
Active Research

This review explores the multifaceted role that iron has in cancer biology. Epidemiological studies have demonstrated an association between excess iron and increased cancer incidence and risk, while experimental studies have implicated iron in cancer initiation, tumor growth, and metastasis. The roles of iron in proliferation, metabolism, and metastasis underpin the association of iron with tumor growth and progression. Cancer cells exhibit an iron-seeking phenotype achieved through dysregulation of iron metabolic proteins. These changes are mediated, at least in part, by oncogenes and tumor suppressors. The dependence of cancer cells on iron has implications in a number of cell death pathways, including ferroptosis, an iron-dependent form of cell death. Uniquely, both iron excess and iron depletion can be utilized in anticancer therapies. Investigating the efficacy of these therapeutic approaches is an area of active research that promises substantial clinical impact.

Abstract 1853: The Chk1 inhibitor, SRA737, synergizes with niraparib to kill cancer cells via multiple cell death pathways

2018 ◽  
Author(s):  
Laurence Booth ◽  
Jane Roberts ◽  
Andrew Poklepovic ◽  
Ryan J. Hansen ◽  
Bryan Strouse ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cell Death Pathways ◽  
Multiple Cell ◽  
Chk1 Inhibitor
Sign in / Sign up

Export Citation Format

Share Document