New clues for platinum antitumor chemistry: Kinetically controlled metal binding to DNA

Reedijk, Jan

doi:10.1073/pnas.0737293100

Cited by 573 publications

(363 citation statements)

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“…In addition, tumour cells develop mechanisms to overcome death signals, including the loss of p53 function, overexpression of antiapoptotic Bcl-2 and interference with caspase activation (Gonzalez et al, 2001;Siddik, 2003). The development of new organometallic complexes with lower toxicity and improved activity is important for improved patient treatment options (Reedijk, 2003). In addition, alternative DNA damage-signalling pathways need to be evoked to circumvent the development of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Cisplatin induces a combination of apoptosis and necrosis in human tumour cells (Gonzalez et al, 2001;Reedijk, 2003). Necrosis may occur directly as a result of cisplatin treatment depending on the level of cellular damage induced or as a consequence of an unfinished apoptotic programme (Gonzalez et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Cellular effects include inhibition of DNA synthesis and RNA transcription, which leads to the activation of cell cycle checkpoints and transient S-phase arrest followed by a durable G 2 /M arrest (Shi et al, 1994;Shapiro and Harper, 1999;Gonzalez et al, 2001;Reedijk, 2003;Siddik, 2003). In this study, we investigated the cell cycle effects of novel Titanocenes X and Y.…”

Section: Discussionmentioning

confidence: 99%

“…However, despite this, the antineoplastic effects of cisplatin has generated much interest in developing new organometallic complexes with reduced toxicity and improved clinical activity (Reedijk, 2003). This led to the development of alternative transition metal-based anticancer drugs (Farrell et al, 1999;Gelasco and Lippard, 1999;Jamieson and Lippard, 1999); however, success in this area has been slow.…”

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confidence: 99%

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Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

et al. 2007

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Titanocene compounds are a novel series of agents that exhibit cytotoxic effects in a variety of human cancer cells in vitro and in vivo. In this study, the antiproliferative activity of two titanocenes (Titanocenes X and Y) was evaluated in human epidermoid cancer cells in vitro. Titanocenes X and Y induce apoptotic cell death in epidermoid cancer cells, with IC50 values that are comparable to cisplatin. Characterisation of the cell death pathway induced by titanocene compounds in A431 cells revealed that apoptosis is preceded by cell cycle arrest and the inhibition of cell proliferation. The induction of apoptosis is dependent on the activation of caspase-3 and -7 but not caspase-8. Furthermore, the antitumour activity of Titanocene Y was tested in an A431 xenograft model of epidermoid cancer. Results indicate that Titanocene Y significantly reduced the growth of A431 xenografts with an antitumour effect similar to cisplatin. These results suggest that titanocenes represent a novel series of promising antitumour agents.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

et al. 2007

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“…However, the side-effects of cisplatin chemotherapy and resistance during the course of the treatment limit its clinical use (1)(2)(3). Cisplatin is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis.…”

Section: Introductionmentioning

confidence: 99%

Ammonium chloride enhances cisplatin cytotoxicity through DNA double-strand breaks in human cervical cancer cells

Wang

Ding

et al. 2013

Oncology Reports

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Abstract. Cisplatin (cis-diamminedichloroplatinum II, CDDP) acts as a therapeutic agent by initiating cellular apoptosis. However, side-effects and drug resistance limit the clinical use of cisplatin. Numerous studies have focused on the drug-target interactions, cellular pharmacology and pharmacokinetics of cisplatin. Newly developed treatment strategies are needed in order to be used in combination with cisplatin, with the aim to minimize toxicity and to circumvent cisplatin resistance. Ammonium chloride (NH 4 Cl) is widely used in various areas, but its use as a combination agent with cisplatin for the treatment of cancer cells has not been previously reported. In the present study, we showed that NH 4 Cl could be potentially used as an effective agent in cisplatin combination treatment of HeLa human cervical cancer (HCC) cells. Cisplatin was found to inhibit cell growth, as well as to induce cell apoptosis and DNA double-strand breaks. In addition, treatment with NH 4 Cl increased the rate of cell apoptosis and the activation of caspase-3. Particularly, we found that NH 4 Cl treatment increased cisplatin-induced phosphorylation of H 2 AX. In conclusion, our data indicate that NH 4 Cl enhances cisplatin cytotoxicity through increased DNA damage in HeLa HCC cells. IntroductionCisplatin (cis-diamminedichloroplatinum II, CDDP) is one of the most effective chemotherapeutic agents widely used for the treatment of solid tumors. However, the side-effects of cisplatin chemotherapy and resistance during the course of the treatment limit its clinical use (1-3). Cisplatin is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death predominantly by inducing apoptosis (4). Based on the mechanism of action of cisplatin-induced cell death, modifications to the combination methods used in chemotherapy are required to reduce the side-effects and increase the therapeutic effects of cisplatin. Autophagy inhibitors, such as 3-methyladenine and chloroquine, have been shown to effectively enhance cisplatin cytotoxity (5-8). Additional agents have been recently assessed such as bortezomib (PS-341, Velcade), a proteasome inhibitor (9,10), and histone acetyltransferase inhibitor, suberoylanilide hydroxamic acid (SAHA) (11,12). Some of these agents have been shown to confer sensitizing effects to cisplatin combination therapy.Ammonium chloride (NH 4 Cl) is an agent used for the treatment of metabolic alkalosis in clinical practice (13). NH 4 Cl was recently used as an autophagy inhibitor in in vitro studies, where it was found to affect the pH of lysosomes and to disturb the activity of autolysosomes (14-16). In the present study, we used NH 4 Cl combined with cisplatin to investigate the potentially effective use of NH 4 Cl as an agent in cisplatin combination chemotherapy.In the present study, we tested the hypothesis that the use of NH 4 Cl increases the apoptosis induced by cispl...

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Nucleic Acid–Metal Ion Interactions

Kazakov

Hecht

2005

Encyclopedia of Inorganic Chemistry

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Nucleic acids (DNA and RNA) are actually salts (or complexes) of metal ions from a chemical point of view. It is impossible to separate the behavior of DNA and RNA from their interactions with metal ions. Metal ions are usually required to promote and stabilize functionally active or native conformations of nucleic acids, as well as to mediate nucleic acid‐protein interactions. However, certain metal ions can also cause structural transformation of nucleic acids, and induce their chemical modification and cleavage. Metal‐nucleic acid interactions are involved in nucleotide biochemistry; genetic information storage and transfer, and control of gene expression, as well as in mutagenesis and carcinogenesis. However, in most cases, it is not currently clear whether the observed effects actually result from direct metal ion‐nucleic acid interaction, since other species, such as specific proteins, may be mediators between the metal ion and the nucleic acid in these processes in vivo . Interest in metal‐nucleic acid interactions is also enhanced by studies of the mechanisms of antitumor activity of certain platinum metal compounds, finding metal ions in crystal structure of natural RNA molecules, studies of the mechanism of RNA catalysis and possible involvement of metal ions in origin of life, as well as by the use of metal ions as structural probes of nucleic acids and as biotechnology tools. This article does not attempt to be comprehensive, but rather presents selected examples to illustrate key facets of metal ion‐nucleic acid interaction. The focus is on the chemical and structural properties of both nucleic acids and metal ions relevant to their interactions. Nucleic acid‐metal interactions can be either nonspecific or dependent on the chemical nature, sequence, and structure of nucleic acids. However, the specificity of these interactions is dependent on structural and chemical properties of both the nucleic acids and the metal ions. Both nucleic acids and metal ions exhibit considerable complexity in their interactions, and such interactions could affect the chemical and biochemical properties of both species.

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New clues for platinum antitumor chemistry: Kinetically controlled metal binding to DNA

Cited by 573 publications

References 91 publications

Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

Ammonium chloride enhances cisplatin cytotoxicity through DNA double-strand breaks in human cervical cancer cells

Nucleic Acid–Metal Ion Interactions

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