Inhibition of transcription by platinum antitumor compounds

Todd, Ryan C.; Lippard, Stephen J.

doi:10.1039/b907567d

Cited by 483 publications

(374 citation statements)

References 144 publications

(258 reference statements)

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“…cDDP cytotoxicity is thought to be mediated in part by the conjugation of the cDDP platinum moiety to nuclear DNA, leading to intrastrand DNA cross-linking followed by cellular apoptosis (15). One possible mechanism of resistance could be that undepleted MNT-1 melanoma cells have a more rapid rate of DNA repair compared with depleted cells.…”

Section: Depletion Of Vps33a or Cno Resulted In Increased Melanoma Cellmentioning

confidence: 99%

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

Huang

Chinen

Chang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis-diaminedichloroplatinum II (cDDP, cis-platin), carboplatin, dacarbazine, or temozolomide together with velaparib, an inhibitor of poly (ADP ribose) polymerase 1, is increased by up to 10-fold by targeting genes that regulate both protein trafficking and the formation of melanosomes, intracellular organelles unique to melanocytes and melanoma cells. Melanoma cells depleted of either of the proteintrafficking regulators vacuolar protein sorting 33A protein (VPS33A) or cappuccino protein (CNO) have increased nuclear localization of cDDP, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. Depleted cells also exhibit a decreased proportion of intracellular, mature melanosomes compared with undepleted cells. Modulation of protein trafficking via cell-surface signaling by binding the melanocortin 1 receptor with the antagonist agouti-signaling protein decreased the proportion of mature melanosomes formed and increased cDDP sensitivity, whereas receptor binding with the agonist melanocytestimulating hormone resulted in an increased proportion of mature melanosomes formed and in decreased sensitivity (i.e., increased resistance) to cDDP. Mutation of the protein-trafficking gene Hps6, known to impair the formation of mature melanosomes, also increased cDDP sensitivity. Together, these results indicate that targeting protein-trafficking molecules markedly increases melanoma treatment sensitivity and influences the degree of melanosomes available for sequestration of therapeutic agents.

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Section: Depletion Of Vps33a or Cno Resulted In Increased Melanoma Cellmentioning

confidence: 99%

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

Huang

Chinen

Chang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Upon administration of satraplatin, a number of metabolites (JM118, JM383, JM518, JM559 and JM149) are formed [43]. Satraplatin and other platinum-based compounds exhibit anti-tumour activity via the formation of DNA crosslinks in vitro [44] which in turn results in specific cellular responses, namely, apoptosis and inhibition of transcription leading to arrest of cell replication [45][46][47]. It has been amply demonstrated that the primary mechanism of cell death induced by platinum compounds is through the formation of DNA adducts [45,48,49].…”

Section: Discussionmentioning

confidence: 99%

<i>In Vitro</i> Investigation of DNA Damage Induced by the DNA Cross-Linking Agents Oxaliplatin and Satraplatin in Lymphocytes of Colorectal Cancer Patients

Alotaibi¹,

Baumgartner²,

Najafzadeh³

et al. 2012

JCT

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Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can induce mutations, chromosomal rearrangements, and cell death. Many DNA interstrand crosslinks lesions can be generated by platinum-based chemotherapeutic agents. Satraplatin is a novel orally administered platinum-based chemotherapeutic agent. In the present study, we investigated DNA interstrand crosslinks lesions induced by oxaliplatin and satraplatin in lymphocytes obtained from colorectal cancer patients and healthy volunteers. Satraplatin demonstrated an increase in interstrand crosslinks in a dose-dependent manner in the Comet assay (p < 0.001). In addition, satraplatin and oxaliplatin increased significantly the number of sister chromatid exchanges up to 8.5-fold and 5.1-fold (p < 0.001) respectively, when treated with 2 µM concentration in comparison to untreated colorectal cancer cells. Further, the γH2AX foci formation was investigated by an immunofluorescence assay with oxaliplatin and satraplatin. The γH2AX foci formation rate was increased by approximately 9-fold when lymphocytes were treated with 2 μM oxaliplatin. Satraplatin was found to significantly induce the number of γH2AX foci by 8.5-fold and 11-fold with both 0.2 μM and 2.0 μM, respectively, compared to the control volunteers that may indicate the repair system in cancer cells experiences a loss of ability to cope with the repair of DSBs. In conclusion, oxaliplatin and satraplatin effectively induced DNA interstrand crosslinks in lymphocytes obtained from colorectal cancer patients and healthy volunteers in vitro. Here, to the best of our knowledge we report for the first time evidence of DNA double strand breaks formation as a possible molecular mechanism of action for satraplatin.

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“…57,58 The helix of DNA being greatly distorted with the covalent binding of cisplatin, 51,52 we speculate that such binding may shorten the distance of C5′-H or even C3′-H to the guanine radical and make H abstraction more feasible than in regular DNA, thus increasing the yields of SSB or DSB. Since at low Pt ratios, in supercoiled DNA, Pt drugs form a considerable quantity of interstrand CL between guanines in opposite strands, 28 the simultaneous formation of two guanine radicals by a single LEE could induce a DSB by a single-hit process with considerable efficiency (Figure 6c).…”

Section: Modification Of the Dsb Yield Function By Cisplatin: Breamentioning

confidence: 98%

Cisplatin Radiosensitization of DNA Irradiated with 2–20 eV Electrons: Role of Transient Anions

et al. 2014

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Platinum chemotherapeutic agents, such as cisplatin (cis-diamminedichloroplatinum(II)), can act as radiosensitizers when bound covalently to nuclear DNA in cancer cells. This radiosensitization is largely due to an increase in DNA damage induced by low-energy secondary electrons, produced in large quantities by high-energy radiation. We report the yields of single-and doublestrand breaks (SSB and DSB) and interduplex cross-links (CL) induced by electrons of 1.6-19.6 eV (i.e., the yield functions) incident on 5 monolayer (ML) films of cisplatin-DNA complexes. These yield functions are compared with those previously recorded with 5 ML films of unmodified plasmid DNA. Binding of five cisplatin molecules to plasmid DNA (3197 base pairs) enhances SSB, DSB, and CL by factors varying, from 1.2 to 2.8, 1.4 to 3.5, and 1.2 to 2.7, respectively, depending on electron energy. All yield functions exhibit structures around 5 and 10 eV that can be attributed to enhancement of bond scission, via the initial formation of core-excited resonances associated with π → π* transitions of the bases. This increase in damage is interpreted as arising from a modification of the parameters of the corresponding transient anions already present in nonmodified DNA, particularly those influencing molecular dissociation. Two additional resonances, specific to cisplatin-modified DNA, are formed at 13.6 and 17.6 eV in the yield function of SSB. Furthermore, cisplatin binding causes the induction of DSB by electrons of 1.6-3.6 eV, i.e., in an energy region where a DSB cannot be produced by a single electron in pure DNA. Breaking two bonds with a subexcitation-energy electron is tentatively explained by a charge delocalization mechanism, where a single electron occupies simultaneously two σ* bonds linking the Pt atom to guanine bases on opposite strands.

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Inhibition of transcription by platinum antitumor compounds

Cited by 483 publications

References 144 publications

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

<i>In Vitro</i> Investigation of DNA Damage Induced by the DNA Cross-Linking Agents Oxaliplatin and Satraplatin in Lymphocytes of Colorectal Cancer Patients

Cisplatin Radiosensitization of DNA Irradiated with 2–20 eV Electrons: Role of Transient Anions

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Inhibition of transcription by platinum antitumor compounds

Cited by 483 publications

References 144 publications

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

&lt;i&gt;In Vitro&lt;/i&gt; Investigation of DNA Damage Induced by the DNA Cross-Linking Agents Oxaliplatin and Satraplatin in Lymphocytes of Colorectal Cancer Patients

Cisplatin Radiosensitization of DNA Irradiated with 2–20 eV Electrons: Role of Transient Anions

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<i>In Vitro</i> Investigation of DNA Damage Induced by the DNA Cross-Linking Agents Oxaliplatin and Satraplatin in Lymphocytes of Colorectal Cancer Patients