Abstract 3334: GSTP1-activated nitric oxide-releasing/PARP inhibitor hybrid prodrugs induce cancer cell death through ROS/RNS, DNA damage, ER stress, and apoptosis.

2013 ◽  
Author(s):  
Anna E. Maciag ◽  
Joseph E. Saavedra ◽  
Ryan J. Holland ◽  
Youseung Kim ◽  
Vandana Kumari ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Parp Inhibitor ◽  
Cancer Cell Death ◽  
Nitric Oxide Releasing

scholarly journals Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

Redox Biology ◽  
2013 ◽  
Vol 1 (1) ◽  
pp. 115-124 ◽  
Author(s):  
Anna E. Maciag ◽  
Ryan J. Holland ◽  
Y.-S. Robert Cheng ◽  
Luis G. Rodriguez ◽  
Joseph E. Saavedra ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Cancer Cell ◽  
Redox Balance ◽  
Cellular Redox ◽  
Cancer Cell Death ◽  
Nitric Oxide Releasing

scholarly journals An Interaction with PARP-1 and Inhibition of Parylation Contribute to Attenuation of DNA Damage Signaling by the Adenovirus E4orf4 Protein

2019 ◽  
Vol 93 (19) ◽  
Author(s):  
Keren Nebenzahl-Sharon ◽  
Rakefet Sharf ◽  
Jana Amer ◽  
Hassan Shalata ◽  
Hanan Khoury-Haddad ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cancer Cell ◽  
Virus Replication ◽  
Parp Inhibitor ◽  
Dependent Manner ◽  
Drug Induced ◽  
Cancer Cell Death ◽  
Dna Damage Signaling ◽  
Parp 1

ABSTRACT The adenovirus (Ad) E4orf4 protein was reported to contribute to inhibition of ATM- and ATR-regulated DNA damage signaling during Ad infection and following treatment with DNA-damaging drugs. Inhibition of these pathways improved Ad replication, and when expressed alone, E4orf4 sensitized transformed cells to drug-induced toxicity. However, the mechanisms utilized were not identified. Here, we show that E4orf4 associates with the DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP-1) and that the association requires PARP activity. During Ad infection, PARP is activated, but its activity is not required for recruitment of either E4orf4 or PARP-1 to virus replication centers, suggesting that their association occurs following recruitment. Inhibition of PARP-1 assists E4orf4 in reducing DNA damage signaling during infection, and E4orf4 attenuates virus- and DNA damage-induced parylation. Furthermore, E4orf4 reduces PARP-1 phosphorylation on serine residues, which likely contributes to PARP-1 inhibition as phosphorylation of this enzyme was reported to enhance its activity. PARP-1 inhibition is important to Ad infection since treatment with a PARP inhibitor enhances replication efficiency. When E4orf4 is expressed alone, it associates with poly(ADP-ribose) (PAR) chains and is recruited to DNA damage sites in a PARP-1-dependent manner. This recruitment is required for inhibition of drug-induced ATR signaling by E4orf4 and for E4orf4-induced cancer cell death. Thus, the results presented here demonstrate a novel mechanism by which E4orf4 targets and inhibits DNA damage signaling through an association with PARP-1 for the benefit of the virus and impacting E4orf4-induced cancer cell death. IMPORTANCE Replication intermediates and ends of viral DNA genomes can be recognized by the cellular DNA damage response (DDR) network as DNA damage whose repair may lead to inhibition of virus replication. Therefore, many viruses evolved mechanisms to inhibit the DDR network. We have previously shown that the adenovirus (Ad) E4orf4 protein inhibits DDR signaling, but the mechanisms were not identified. Here, we describe an association of E4orf4 with the DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP-1). E4orf4 reduces phosphorylation of this enzyme and inhibits its activity. PARP-1 inhibition assists E4orf4 in reducing Ad-induced DDR signaling and improves the efficiency of virus replication. Furthermore, the ability of E4orf4, when expressed alone, to accumulate at DNA damage sites and to kill cancer cells is attenuated by chemical inhibition of PARP-1. Our results indicate that the E4orf4–PARP-1 interaction has an important role in Ad replication and in promotion of E4orf4-induced cancer-selective cell death.

Water-Soluble Dinitrosyl Iron Complex (DNIC): a Nitric Oxide Vehicle Triggering Cancer Cell Death via Apoptosis

2016 ◽  
Vol 55 (18) ◽  
pp. 9383-9392 ◽  
Author(s):  
Shou-Cheng Wu ◽  
Chung-Yen Lu ◽  
Yi-Lin Chen ◽  
Feng-Chun Lo ◽  
Ting-Yin Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Cancer Cell ◽  
Iron Complex ◽  
Water Soluble ◽  
Dinitrosyl Iron Complex ◽  
Cancer Cell Death ◽  
Dinitrosyl Iron

γ-Tocotrienol-induced endoplasmic reticulum stress and autophagy act concurrently to promote breast cancer cell death

2015 ◽  
Vol 93 (4) ◽  
pp. 306-320 ◽  
Author(s):  
Roshan V. Tiwari ◽  
Parash Parajuli ◽  
Paul W. Sylvester
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Human Breast Cancer ◽  
Beclin 1 ◽  
Time Dependent ◽  
Human Breast ◽  
Cancer Cell Death

The anticancer effects of γ-tocotrienol are associated with the induction of autophagy and endoplasmic reticulum (ER) stress-mediated apoptosis, but a direct relationship between these events has not been established. Treatment with 40 μmol/L of γ-tocotrienol caused a time-dependent decrease in cancer cell viability that corresponds to a concurrent increase in autophagic and endoplasmic reticulum (ER) stress markers in MCF-7 and MDA-MB-231 human breast cancer cells. γ-Tocotrienol treatment was found to cause a time-dependent increase in early phase (Beclin-1, LC3B-II) and late phase (LAMP-1 and cathepsin-D) autophagy markers, and pretreatment with autophagy inhibitors Beclin-1 siRNA, 3-MA or Baf1 blocked these effects. Furthermore, blockage of γ-tocotrienol-induced autophagy with Beclin-1 siRNA, 3-MA, or Baf1 induced a modest, but significant, reduction in γ-tocotrienol-induced cytotoxicity. γ-Tocotrienol treatment was also found to cause a decrease in mitogenic Erk1/2 signaling, an increase in stress-dependent p38 and JNK1/2 signaling, as well as an increase in ER stress apoptotic markers, including phospho-PERK, phospho-eIF2α, Bip, IRE1α, ATF-4, CHOP, and TRB3. In summary, these finding demonstrate that γ-tocotrienol-induced ER stress and autophagy occur concurrently, and together act to promote human breast cancer cell death.

scholarly journals Statin-Induced Breast Cancer Cell Death: Role of Inducible Nitric Oxide and Arginase-Dependent Pathways

2007 ◽  
Vol 67 (15) ◽  
pp. 7386-7394 ◽  
Author(s):  
Srigiridhar Kotamraju ◽  
Carol L. Willams ◽  
Balaraman Kalyanaraman
Keyword(s):  
Breast Cancer ◽  
Nitric Oxide ◽  
Cell Death ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Death ◽  
Inducible Nitric Oxide

New Fe(iii) and Co(ii) salen complexes with pendant distamycins: selective targeting of cancer cells by DNA damage and mitochondrial pathways

2016 ◽  
Vol 45 (22) ◽  
pp. 9345-9353 ◽  
Author(s):  
Asfa Ali ◽  
Mohini Kamra ◽  
Arunoday Bhan ◽  
Subhrangsu S. Mandal ◽  
Santanu Bhattacharya
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Metal Complexes ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Death ◽  
Salen Complexes ◽  
Selective Targeting

Distamycin like moieties conjugated with core Fe(iii) and Co(ii) based salens were synthesized and studied. The metal complexes showed better and differential activity toward cancer cell death.

scholarly journals GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation

2021 ◽  
Vol 22 (2) ◽  
pp. 622
Author(s):  
Mikhail G. Akimov ◽  
Alina M. Gamisonia ◽  
Polina V. Dudina ◽  
Natalia M. Gretskaya ◽  
Anastasia A. Gaydaryova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Nitric Oxide Synthase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Receptor Activation ◽  
Gene Expression Measurement ◽  
Fatty Acid Amides ◽  
Cancer Cell Death ◽  
Oxide Synthase

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca2+, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.

Abstract 1234: The anticancer drug ABTL0812 induces cancer cell death by impairing Akt/mTORC1 axis and inducing ER stress-mediated cytotoxic autophagy

2020 ◽  
Author(s):  
Pau Muñoz-Guardiola ◽  
Josefina Casas ◽  
Elisabet Megías-Roda ◽  
Hector Perez-Montoyo ◽  
Sonia Solé-Sánchez ◽  
...  
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Cancer Cell Death
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