Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2-deoxycitidine and 1-h-D-Arabinofuranoside

Abeer A.bd Elmoneim; Elisabeth Heuston; Daniel H. Wai; Timothy Triche; Robert J. Arceci

Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2-deoxycitidine and 1-h-D-Arabinofuranoside

Abeer A.bd Elmoneim, Elisabeth Heuston, Daniel H. Wai, Timothy Triche, Robert J. Arceci

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: The search for synergistic drug combinations is critical to the treatment of drug-resistant cancer, such as acute myeloid leukemia (AML). Characterizing RNA expression associated with 5-aza-2'-deoxycytidine (DAC) and 1-h-D-arabinofuranosylcytosine (Ara-C) is a critical step to increase the efficacy of their combinatorial therapies.

MATERIALS AND METHODS: After 72 h of single-dose treatments of AML cells with DAC or Ara-C, the half-maximal effective concentration of DAC and Ara-C and the drug combination index were assessed.

RESULTS: Pre-treatment with DAC restores cellular sensitivity in Ara-C-resistant AML cells. In contrast, DAC/Ara-C combinations are antagonistic in other Ara-C-sensitive AML cells.

CONCLUSION: Our results provide an alternative approach for predicting what combinations, dosing and scheduling of drug delivery should be used to better individualize therapy of AML.

Original language	English (US)
Pages (from-to)	691-696
Number of pages	6
Journal	Anticancer research
Volume	36
Issue number	2
State	Published - Feb 1 2016

Keywords

Drug interaction
myeloid leukemia
pediatric cancer

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

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title = "Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2-deoxycitidine and 1-h-D-Arabinofuranoside",

abstract = "BACKGROUND: The search for synergistic drug combinations is critical to the treatment of drug-resistant cancer, such as acute myeloid leukemia (AML). Characterizing RNA expression associated with 5-aza-2'-deoxycytidine (DAC) and 1-h-D-arabinofuranosylcytosine (Ara-C) is a critical step to increase the efficacy of their combinatorial therapies.MATERIALS AND METHODS: After 72 h of single-dose treatments of AML cells with DAC or Ara-C, the half-maximal effective concentration of DAC and Ara-C and the drug combination index were assessed.RESULTS: Pre-treatment with DAC restores cellular sensitivity in Ara-C-resistant AML cells. In contrast, DAC/Ara-C combinations are antagonistic in other Ara-C-sensitive AML cells.CONCLUSION: Our results provide an alternative approach for predicting what combinations, dosing and scheduling of drug delivery should be used to better individualize therapy of AML.",

keywords = "Drug interaction, myeloid leukemia, pediatric cancer",

author = "Elmoneim, {Abeer A.bd} and Elisabeth Heuston and Wai, {Daniel H.} and Timothy Triche and Arceci, {Robert J.}",

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language = "English (US)",

volume = "36",

pages = "691--696",

journal = "Anticancer research",

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T1 - Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2-deoxycitidine and 1-h-D-Arabinofuranoside

AU - Elmoneim, Abeer A.bd

AU - Heuston, Elisabeth

AU - Wai, Daniel H.

AU - Triche, Timothy

AU - Arceci, Robert J.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - BACKGROUND: The search for synergistic drug combinations is critical to the treatment of drug-resistant cancer, such as acute myeloid leukemia (AML). Characterizing RNA expression associated with 5-aza-2'-deoxycytidine (DAC) and 1-h-D-arabinofuranosylcytosine (Ara-C) is a critical step to increase the efficacy of their combinatorial therapies.MATERIALS AND METHODS: After 72 h of single-dose treatments of AML cells with DAC or Ara-C, the half-maximal effective concentration of DAC and Ara-C and the drug combination index were assessed.RESULTS: Pre-treatment with DAC restores cellular sensitivity in Ara-C-resistant AML cells. In contrast, DAC/Ara-C combinations are antagonistic in other Ara-C-sensitive AML cells.CONCLUSION: Our results provide an alternative approach for predicting what combinations, dosing and scheduling of drug delivery should be used to better individualize therapy of AML.

AB - BACKGROUND: The search for synergistic drug combinations is critical to the treatment of drug-resistant cancer, such as acute myeloid leukemia (AML). Characterizing RNA expression associated with 5-aza-2'-deoxycytidine (DAC) and 1-h-D-arabinofuranosylcytosine (Ara-C) is a critical step to increase the efficacy of their combinatorial therapies.MATERIALS AND METHODS: After 72 h of single-dose treatments of AML cells with DAC or Ara-C, the half-maximal effective concentration of DAC and Ara-C and the drug combination index were assessed.RESULTS: Pre-treatment with DAC restores cellular sensitivity in Ara-C-resistant AML cells. In contrast, DAC/Ara-C combinations are antagonistic in other Ara-C-sensitive AML cells.CONCLUSION: Our results provide an alternative approach for predicting what combinations, dosing and scheduling of drug delivery should be used to better individualize therapy of AML.

KW - Drug interaction

KW - myeloid leukemia

KW - pediatric cancer

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IS - 2

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Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2-deoxycitidine and 1-h-D-Arabinofuranoside

Abstract

Keywords

ASJC Scopus subject areas

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