Effective cytotoxicity against human leukemias and chemotherapy-resistant leukemia cell lines by N-N-dimethylsphingosine

David B. Jendiroba; Jim Klostergaard; Afsaneh Keyhani; Lance Pagliaro; Emil J. Freireich

doi:10.1016/S0145-2126(01)00129-1

Effective cytotoxicity against human leukemias and chemotherapy-resistant leukemia cell lines by N-N-dimethylsphingosine

David B. Jendiroba
, Jim Klostergaard
, Afsaneh Keyhani
, Lance Pagliaro
, Emil J. Freireich

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

29 Scopus citations

Abstract

We evaluated the cytotoxicity of dimethylsphingosine (DMS) against four human leukemia cell lines: two acute (HL60 and a multi-drug resistance MDR-positive derivative HL60-dox) and two blast crisis chronic myelogenous leukemias (JFP1, from a treatment refractory patient and K562), and against blasts isolated from 11 leukemia patients. Cell line viability decreased proportionally to DMS concentration and treatment time (P<0.001). HL60-dox and JFP1 were the most sensitive, indicating DMS efficacy against human leukemia MDR. Importantly, leukemia samples showed a similar sensitivity to DMS as that of the cell lines, firstly demonstrating PKC-independent sphingolipid activity against fresh human tumor specimens. DMS-based chemotherapy may improve leukemia treatment.

Original language	English (US)
Pages (from-to)	301-310
Number of pages	10
Journal	Leukemia Research
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/S0145-2126(01)00129-1
State	Published - 2002

Keywords

Cytotoxicity
Dimethylsphingosine
Leukemia patients
Sphingolipids

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1016/S0145-2126(01)00129-1

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title = "Effective cytotoxicity against human leukemias and chemotherapy-resistant leukemia cell lines by N-N-dimethylsphingosine",

abstract = "We evaluated the cytotoxicity of dimethylsphingosine (DMS) against four human leukemia cell lines: two acute (HL60 and a multi-drug resistance MDR-positive derivative HL60-dox) and two blast crisis chronic myelogenous leukemias (JFP1, from a treatment refractory patient and K562), and against blasts isolated from 11 leukemia patients. Cell line viability decreased proportionally to DMS concentration and treatment time (P<0.001). HL60-dox and JFP1 were the most sensitive, indicating DMS efficacy against human leukemia MDR. Importantly, leukemia samples showed a similar sensitivity to DMS as that of the cell lines, firstly demonstrating PKC-independent sphingolipid activity against fresh human tumor specimens. DMS-based chemotherapy may improve leukemia treatment.",

keywords = "Cytotoxicity, Dimethylsphingosine, Leukemia patients, Sphingolipids",

author = "Jendiroba, \{David B.\} and Jim Klostergaard and Afsaneh Keyhani and Lance Pagliaro and Freireich, \{Emil J.\}",

note = "Funding Information: The authors want to thank Lorraine A. Joyce and Kathy Tucker for assistance with the manuscript. This work was supported in part by The Cancer Research Foundation of North Texas, Arlington, TX. D. Jendiroba and J. Klostergaard provided the concept, design, analysis, and interpretation of the data and drafted and revised the article. In addition, D. Jendiroba collected, assembled the data, and provided statistical expertise, whereas J. Klostergaard provided study materials and gave final approval. A. Keyhani contributed to the concept and design, analyzed the data, and provided logistical support. L. Pagliaro contributed to the concept and design, provided critical revision of the paper, provided study materials, and obtained the necessary funding. E.J. Freireich contributed significantly to the concept, design, interpretation of the data, critical input to the revision, obtained some of the necessary funding, and gave final approval. ",

year = "2002",

doi = "10.1016/S0145-2126(01)00129-1",

language = "English (US)",

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T1 - Effective cytotoxicity against human leukemias and chemotherapy-resistant leukemia cell lines by N-N-dimethylsphingosine

AU - Jendiroba, David B.

AU - Klostergaard, Jim

AU - Keyhani, Afsaneh

AU - Pagliaro, Lance

AU - Freireich, Emil J.

N1 - Funding Information: The authors want to thank Lorraine A. Joyce and Kathy Tucker for assistance with the manuscript. This work was supported in part by The Cancer Research Foundation of North Texas, Arlington, TX. D. Jendiroba and J. Klostergaard provided the concept, design, analysis, and interpretation of the data and drafted and revised the article. In addition, D. Jendiroba collected, assembled the data, and provided statistical expertise, whereas J. Klostergaard provided study materials and gave final approval. A. Keyhani contributed to the concept and design, analyzed the data, and provided logistical support. L. Pagliaro contributed to the concept and design, provided critical revision of the paper, provided study materials, and obtained the necessary funding. E.J. Freireich contributed significantly to the concept, design, interpretation of the data, critical input to the revision, obtained some of the necessary funding, and gave final approval.

PY - 2002

Y1 - 2002

N2 - We evaluated the cytotoxicity of dimethylsphingosine (DMS) against four human leukemia cell lines: two acute (HL60 and a multi-drug resistance MDR-positive derivative HL60-dox) and two blast crisis chronic myelogenous leukemias (JFP1, from a treatment refractory patient and K562), and against blasts isolated from 11 leukemia patients. Cell line viability decreased proportionally to DMS concentration and treatment time (P<0.001). HL60-dox and JFP1 were the most sensitive, indicating DMS efficacy against human leukemia MDR. Importantly, leukemia samples showed a similar sensitivity to DMS as that of the cell lines, firstly demonstrating PKC-independent sphingolipid activity against fresh human tumor specimens. DMS-based chemotherapy may improve leukemia treatment.

AB - We evaluated the cytotoxicity of dimethylsphingosine (DMS) against four human leukemia cell lines: two acute (HL60 and a multi-drug resistance MDR-positive derivative HL60-dox) and two blast crisis chronic myelogenous leukemias (JFP1, from a treatment refractory patient and K562), and against blasts isolated from 11 leukemia patients. Cell line viability decreased proportionally to DMS concentration and treatment time (P<0.001). HL60-dox and JFP1 were the most sensitive, indicating DMS efficacy against human leukemia MDR. Importantly, leukemia samples showed a similar sensitivity to DMS as that of the cell lines, firstly demonstrating PKC-independent sphingolipid activity against fresh human tumor specimens. DMS-based chemotherapy may improve leukemia treatment.

KW - Cytotoxicity

KW - Dimethylsphingosine

KW - Leukemia patients

KW - Sphingolipids

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Effective cytotoxicity against human leukemias and chemotherapy-resistant leukemia cell lines by N-N-dimethylsphingosine

Abstract

Keywords

ASJC Scopus subject areas

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