Antitumor activity of TMPyP4 interacting G-quadruplex in retinoblastoma cell lines

Mikami-Terao, Yoko; Akiyama, Masaharu; Yuza, Yuki; Yanagisawa, Takaaki; Kawano, Takeshi; Agawa, Miyuki; Ida, Hiroyuki

doi:10.1016/j.exer.2009.03.008

Cited by 41 publications

(34 citation statements)

References 27 publications

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“…Preliminary studies using the MTS assay [31] investigated the cytotoxicity of complex 6, the complex with the best selectivity for G4 versus duplex DNA, in telomerase-expressing cancer cell lines A549 and MCF-7, as well as in a normal fibroblast cell line, MRC-5. Complex 6 was found to be threefold more cytotoxic to the cancer cell lines than to the normal fibroblast cell line (IC 50 values of~20 mm versus 60 mm upon treatment for 72 h).…”

Section: Preliminary Cytotoxicity Studiesmentioning

confidence: 99%

Platinum(II) Phenanthroimidazoles for Targeting Telomeric G‐Quadruplexes

et al. 2011

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A rationally designed progression of phenanthroimidazole platinum(II) complexes were examined for their ability to target telomere-derived intramolecular G-quadruplex DNA. Through the use of circular dichroism, fluorescence displacement assays, and molecular modeling we show that these complexes template and stabilize G-quadruplexes from sequences based on the human telomeric repeat (TTAGGG)(n). The greatest stabilization was observed for the p-chlorophenyl derivative 6((G4)DC(50) =0.31 μM). We also show that the G-quadruplex binding complexes are able to inhibit telomerase activity through a modified telomerase repeat amplification protocol (TRAP-LIG assay). Preliminary cell studies show that complex 6 is preferentially cytotoxic toward cancer over normal cell lines, indicating its potential use in cancer therapy.

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Section: Preliminary Cytotoxicity Studiesmentioning

confidence: 99%

Platinum(II) Phenanthroimidazoles for Targeting Telomeric G‐Quadruplexes

et al. 2011

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“…308 The mechanisms responsible for biological effects of DNA guanine-quadruplex stabilization induced by the interactive agent TMPyP4 were further investigated and an important role for phosphorylation of histone H2AX (Ser139) and other biologically important proteins (p53, α tubulin and others) was revealed using retinoblastoma cell lines. 309,310 Moreover, increased expression of p21CIP1 and p57KIP2 proteins, and activated MAP kinases (p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and extracellular signal-regulated kinase) were identified in K562 leukemic cells. TMPyP4 treatment significantly inhibited growth, and induced cell cycle arrest and cell death.…”

Section: Porphyrin and Expanded Porphyrin Applications For Combinementioning

confidence: 98%

“…In addition, following treatment a significant enhancement of radiosensitivity was observed, the precise mechanism of which still remains unclear. 309 Nevertheless, a low dose of irradiation seems to be sufficient to induce apoptosis. This fact indicates new potential for this approach for possible reduction in the radiotherapy dose and for removal of unwanted side effects.…”

Section: Porphyrin and Expanded Porphyrin Applications For Combinementioning

confidence: 99%

Design, Synthesis, Selective Recognition Properties and Targeted Drug Delivery Application

Králová¹,

Kejík²,

Břı́za³

et al. 2014

Handbook of Porphyrin Science

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“…Nevertheless, the compound shows some remarkable growth inhibitory properties in an array of cell lines and cancer models. TMPyP4 significantly impairs the growth of K562 leukemia [169] and retinoblastoma cells [170], causing telomerase inhibition and a telomere-induced DNA damage response in both cases. It also induces telomere shortening in osteosarcoma cells leading to apoptosis [171].…”

Section: Tmpyp4mentioning

confidence: 99%

G-quadruplex interacting small molecules and drugs: from bench toward bedside

Müller

Rodriguez

2014

Expert Review of Clinical Pharmacology

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G-quadruplexes are non-Watson-Crick four-stranded nucleic acid structures. Recent evidence points toward their existence in vivo and their implication in various biological processes. Over the past two decades, small molecules have been developed to specifically and selectively target these structures in order to dissect mechanisms they have been linked to. This has led to the development of potential therapeutic agents, particularly for anti-carcinogenic activity. Here, we first present how major biological roles of G-quadruplexes have been uncovered by the use of specifically designed small molecule probes. We use this to highlight how fundamental research has contributed to identifying biological functions of G-quadruplexes and their potential as therapeutic targets. We then discuss the development of G-quadruplex interacting small molecules as potential drug candidates.

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Antitumor activity of TMPyP4 interacting G-quadruplex in retinoblastoma cell lines

Cited by 41 publications

References 27 publications

Platinum(II) Phenanthroimidazoles for Targeting Telomeric G‐Quadruplexes

Platinum(II) Phenanthroimidazoles for Targeting Telomeric G‐Quadruplexes

Design, Synthesis, Selective Recognition Properties and Targeted Drug Delivery Application

G-quadruplex interacting small molecules and drugs: from bench toward bedside

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