Water-Soluble Ruthenium(II) Complexes with Chiral 4-(2,3-Dihydroxypropyl)-formamide Oxoaporphine (FOA): In Vitro and in Vivo Anticancer Activity by Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity, and Induction of Tumor Cell Apoptosis

Indocyanine green labeled recombinant annexin V probes (ICG–EGFP–Annexin V and ICG–mPlum–Annexin V) were synthesized for near-infrared and visible fluorescence imaging of tumor cell apoptosis both in vitro and in vivo.

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Abstract 3050: Multimeric IgM antibodies targeting DR5 are potent and rapid inducers of tumor cell apoptosis and cell death in vitro and in vivo

10.1158/1538-7445.am2019-3050 ◽

2019 ◽

Author(s):

Beatrice Wang ◽

Tasnim Kothambawala ◽

Ling Wang ◽

Avneesh Saini ◽

Ramesh Baliga ◽

...

Keyword(s):

Cell Death ◽

Tumor Cell ◽

Cell Apoptosis ◽

Tumor Cell Apoptosis ◽

Igm Antibodies

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NDUFA4L2 promotes glioblastoma progression, is associated with poor survival, and can be effectively targeted by apatinib

Cell Death and Disease ◽

10.1038/s41419-021-03646-3 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Zheng Chen ◽

Xiangyu Wei ◽

Xueyi Wang ◽

Xuan Zheng ◽

Bowen Chang ◽

...

Keyword(s):

Tumor Cell ◽

Hypoxia Inducible Factor ◽

Mitochondrial Respiratory Chain ◽

Metabolic Reprogramming ◽

Tumor Cell Apoptosis ◽

Survival Gene ◽

A Subunit ◽

Tumor Types

AbstractNADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2 (NDUFA4L2) is a subunit of Complex I of the mitochondrial respiratory chain, which is important in metabolic reprogramming and oxidative stress in multiple cancers. However, the biological role and molecular regulation of NDUFA4L2 in glioblastoma (GBM) are poorly understood. Here, we found that NDUFA4L2 was significantly upregulated in GBM; the elevated levels were correlated with reduced patient survival. Gene knockdown of NDUFA4L2 inhibited tumor cell proliferation and enhanced apoptosis, while tumor cells initiated protective mitophagy in vitro and in vivo. We used lentivirus to reduce expression levels of NDUFA4L2 protein in GBM cells exposed to mitophagy blockers, which led to a significant enhancement of tumor cell apoptosis in vitro and inhibited the development of xenografted tumors in vivo. In contrast to other tumor types, NDUFA4L2 expression in GBM may not be directly regulated by hypoxia-inducible factor (HIF)-1α, because HIF-1α inhibitors failed to inhibit NDUFA4L2 in GBM. Apatinib was able to effectively target NDUFA4L2 in GBM, presenting an alternative to the use of lentiviruses, which currently cannot be used in humans. Taken together, our data suggest the use of NDUFA4L2 as a potential therapeutic target in GBM and demonstrate a practical treatment approach.

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G-quadruplex DNA drives genomic instability and represents a targetable molecular abnormality in ATRX-deficient malignant glioma

10.1101/347542 ◽

2018 ◽

Author(s):

Yuxiang Wang ◽

Jie Yang ◽

Wei Wu ◽

Rachna Shah ◽

Carla Danussi ◽

...

Keyword(s):

Dna Damage ◽

Malignant Glioma ◽

Model Systems ◽

Copy Number Alterations ◽

Molecular Alteration ◽

Quadruplex Dna ◽

G4 Dna ◽

G Quadruplex

AbstractMutational inactivation of ATRX (α-thalassemia mental retardation X-linked) represents a defining molecular alteration in large subsets of malignant glioma. Yet the pathogenic consequences of ATRX deficiency remain unclear, as do tractable mechanisms for its therapeutic targeting. Here we report that ATRX loss in isogenic glioma model systems induces replication stress and DNA damage by way of G-quadruplex (G4) DNA secondary structure. Moreover, these effects are associated with the acquisition of disease-relevant copy number alterations over time. We then demonstrate, both in vitro and in vivo, that ATRX deficiency selectively enhances DNA damage and cell death following chemical G4 stabilization. Finally, we show that G4 stabilization synergizes with other DNA-damaging therapies, including ionizing radiation, in the ATRX-deficient context. Our findings reveal novel pathogenic mechanisms driven by ATRX deficiency in glioma, while also pointing to tangible strategies for drug development.

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Copper(ii) complexes based on quinoline-derived Schiff-base ligands: synthesis, characterization, HSA/DNA binding ability, and anticancer activity

MedChemComm ◽

10.1039/c8md00223a ◽

2018 ◽

Vol 9 (10) ◽

pp. 1663-1672 ◽

Cited By ~ 5

Author(s):

Kun Hu ◽

Chensi Liu ◽

Jingui Li ◽

Fupei Liang

Keyword(s):

Schiff Base ◽

Dna Binding ◽

Tumor Cell ◽

Anticancer Activity ◽

Hela Cells ◽

Cell Apoptosis ◽

Schiff Base Ligands ◽

Binding Ability ◽

Tumor Cell Apoptosis ◽

Cell Cycles

Three Cu(ii) complexes (C1–C3) were designed and synthesized.C3, in particular, having a ligand derived from benzocaine, exhibited greater selectivity toward HeLa cells, arrested cell cycles, and promoted tumor cell apoptosis.

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