Sodium butyrate enhances the cytotoxic effect of cisplatin by abrogating the cisplatin imposed cell cycle arrest

Koprinarova, Miglena; Markovska, Petya; Iliev, Ivan; Anachkova, Boyka; Russev, George

doi:10.1186/1471-2199-11-49

Cited by 27 publications

(24 citation statements)

References 37 publications

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“…It has been reported that different HDACi sensitize tumor cells towards the killing effect of many anticancer agents (11,(45)(46)(47) and this effect has been attributed to interference with DNA repair pathways (8,11,48) or abrogation of the cell-cycle checkpoints (18)(19)(20). Our results suggest that the accumulation of intracellular ROS-mediated increase in the lesion burden may be the major mechanism by which sodium butyrate enhances the cytotoxicity of MMC-treated cells.…”

Section: Discussionmentioning

confidence: 50%

“…Recently, it has been reported that sodium butyrate could abrogate the G 1 -S checkpoint activated by cisplatin, force cells in S-phase with damaged DNA, and thus, promote cell killing (20). On the other hand, sodium butyrate was not able to abrogate the G 2 phase checkpoint induced in gamma-irradiated HeLa cells (8) indicating that different cell-cycle arrest points have different sensitivities to HDACi modulation.…”

Section: Introductionmentioning

confidence: 99%

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The Inhibitor of Histone Deacetylases Sodium Butyrate Enhances the Cytotoxicity of Mitomycin C

Gospodinov

Popova

Vassileva

et al. 2012

Molecular Cancer Therapeutics

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The use of histone deacetylase inhibitors has been proposed as a promising approach to increase the cell killing effect of DNA damage-inducing drugs in chemotherapy. However, the molecular mechanism of their action remains understudied. In the present article, we have assessed the effect of the histone deacetylase inhibitor sodium butyrate on the DNA damage response induced by the crosslinking agent mitomycin C. Sodium butyrate increased mitomycin C cytotoxicity, but did not impair the repair pathways required to remove mitomycin C-induced lesions as neither the rate of nucleotide excision repair nor the homologous recombination repair rate were diminished. Sodium butyrate treatment abrogated the S-phase cell-cycle checkpoint in mitomycin C-treated cells and induced the G 2 -M checkpoint. However, sodium butyrate treatment alone resulted in accumulation of reactive oxygen species, double-strand breaks in DNA, and apoptosis. These results imply that the accumulation of reactive oxygen species-mediated increase in DNA lesion burden may be the major mechanism by which sodium butyrate enhances the cytotoxicity of mitomycin C. Mol Cancer Ther; 11(10); 2116-26. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 99%

The Inhibitor of Histone Deacetylases Sodium Butyrate Enhances the Cytotoxicity of Mitomycin C

Gospodinov

Popova

Vassileva

et al. 2012

Molecular Cancer Therapeutics

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“…Another HDAC inhibitor, sodium butyrate, also sensitized HeLa cells to cisplatin. [171]. Cells exposed to this drug were about two-fold more sensitive to cisplatin than cells exposed to cisplatin alone.…”

Section: Cisplatinmentioning

confidence: 95%

The Synergistic Effects of DNA-Targeted Chemotherapeutics and Histone Deacetylase Inhibitors As Therapeutic Strategies for Cancer Treatment

Stiborová

Eckschlager

Poljaková³

et al. 2012

CMC

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Histone deacetylase (HDAC) inhibitors are a group of anticancer drugs which cause growth arrest and apoptosis of several tumor cells. HDAC inhibitors have been also found to increase the anticancer efficacy of several treatment modalities i.e. chemotherapy or radiotherapy. Here, we review the literature on combinations of HDAC inhibitors both with ionizing radiation and with other drugs, highlighting DNA-damaging compounds. The results of numerous studies with several types of cancer cells discussed in this review demonstrate that HDAC inhibitors enhance the effect of DNA damaging agents, such as inhibitors of topoisomerases, inhibitors of DNA synthesis, DNA-intercalators and agents covalently modifying DNA (i.e. doxorubicin, etoposid, 5-fluorouracil, cisplatin, melphalan, temozolomide and ellipticine) or of irradiation. Hence, the use of HDAC inhibitors combined with these antitumor drugs or ionizing radiation is a promising tool which may make treatment of patients suffering from many types of cancer more efficient. Several molecular mechanisms are responsible for the observed higher sensitivity of tumor cells towards therapeutic agents elicited by HDAC inhibitors. These mechanisms are discussed also in this review.

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“…Indeed, there has been no definitive study to examine the effect of cisplatin on G1-phase Cdk complexes, particularly in parallel with S- and G2/M-checkpoint responses. Where G1-arrest by cisplatin has been reported, these are largely observed in p53-defective cells (e.g., HeLa cells [15]) and/or at high cisplatin concentrations (e.g., N5 μM [13,15]), the mechanism for which is not understood. Therefore, to examine the potential of G1-checkpoint response with cisplatin, we have undertaken a systematic biochemical and molecular analysis in ovarian p53-proficient A2780 cells, and used DAP as a positive control for G1-arrest and a negative control for S- and G2/M-arrest in this tumor model system [9,16].…”

Section: Introductionmentioning

confidence: 99%

The impact of S- and G2-checkpoint response on the fidelity of G1-arrest by cisplatin and its comparison to a non-cross-resistant platinum(IV) analog

He¹,

Kuang²,

Khokhar³

et al. 2011

Gynecologic Oncology

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Objective Cisplatin is a DNA-damaging antitumor agent that is highly effective in treating ovarian cancer. It activates the p53/p21 pathway for its cytotoxic mode of action, but it does not induce p21-dependent cell cycle arrest in G1. Therefore, we investigated this paradox, and used the model analog DAP as a positive control for p21-dependent G1-arrest. Methods Studies were conducted in p53-proficient ovarian A2780 tumor cells to examine Cdk activity, cell cycle distribution and DNA damage signaling after cisplatin or DAP in combination with the mitotic inhibitor nocodazole. Results Cisplatin consistently induced transient S-phase arrest by inhibiting Cdk2/cyclin A complex in S-phase at 12 h and then a durable G2/M-arrest by inhibiting Cdc2/cyclin B complex at 12–18 h. These inhibitions were associated with Chk1 and Chk2 activation and resultant increase in inhibitory tyrosine phosphorylation of Cdk2 and Cdc2. Cisplatin also potently inhibited G1-phase Cdk4/cyclin D1 and Cdk2/cyclin E activities at ~18 h. In agreement, exposure of cisplatin-treated A2780, HCT-116p53−/− and HCT-116p21−/− tumor cells to nocodazole revealed limited G1-arrest that was dependent on p53 and p21. In contrast, the durable G1-arrest by DAP, which failed to activate Chk1 and Chk2, was unaffected by nocodazole. Conclusions Cisplatin induced G1-arrest, but at an attenuated level. This was primarily due to orchestration of Cdk inhibition in S-phase first, then in G2, and finally in G1 that effectively blocked cells in G2 and prevented cells from progressing and arresting in G1. These studies demonstrate that cisplatin unequivocally activates G1-checkpoint response, but the fidelity of G1-arrest is compromised by Chk1/2 activation and checkpoint response in S- and G2/M-phase.

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Sodium butyrate enhances the cytotoxic effect of cisplatin by abrogating the cisplatin imposed cell cycle arrest

Cited by 27 publications

References 37 publications

The Inhibitor of Histone Deacetylases Sodium Butyrate Enhances the Cytotoxicity of Mitomycin C

The Inhibitor of Histone Deacetylases Sodium Butyrate Enhances the Cytotoxicity of Mitomycin C

The Synergistic Effects of DNA-Targeted Chemotherapeutics and Histone Deacetylase Inhibitors As Therapeutic Strategies for Cancer Treatment

The impact of S- and G2-checkpoint response on the fidelity of G1-arrest by cisplatin and its comparison to a non-cross-resistant platinum(IV) analog

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