Hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid that selectively induce apoptosis in leukemia cells but not in fibroblasts

Anna Galkin, Anu Surakka, Gustav Boije af Gennäs, Timo Ruotsalainen, Kari Kreander, Päivi Tammela, Kaarina Sivonen, Jari Yli-Kauhaluoma, Pia Vuorela

Research output: Contribution to journalArticleScientificpeer-review

Abstract

New apoptosis modulating agents are widely sought, because failure in regulation of apoptosis is associated with many diseases. In this study, we have evaluated apoptosis inducing the potential of ten new hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid. Cancerous leukemia cells (HL-60) and non-malignant fibroblasts (Swiss 3T3) were incubated with test compounds for 24 h and morphologically evaluated. The changes in mitochondrial membrane potential (Delta psi m) and caspase-3 activity were used to confirm the results and to study early induction of apoptosis. Cytotoxicity was determined using the lactate dehydrogenase (LDH) assay and mutagenicity with miniaturized Ames-test. The most potent selective apoptosis inducers were compounds 1c and 1h having IC50 values of 41 and 23 mu M, respectively, in leukemia cells (HL-60) while effects in fibroblasts (Swiss 3T3) were insignificant. Reduction of 6 m and increase in caspase-3 activity were observed already during the first 2 hr in the HL-60 cells treated with compounds 1 c and 1 h. Neither of the compounds was cytotoxic or mutagenic. The results indicate that compounds 1 c and 1 h are selective apoptosis inducers and should be studied further for possible use in cancer therapy. Drug Dev. Res. 69: 185-195, 2008. (C) 2008 Wiley-Liss, Inc.
Original languageEnglish
JournalDrug Development Research
Volume69
Issue number4
Pages (from-to)185-195
Number of pages11
ISSN0272-4391
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy

Cite this

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title = "Hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid that selectively induce apoptosis in leukemia cells but not in fibroblasts",
abstract = "New apoptosis modulating agents are widely sought, because failure in regulation of apoptosis is associated with many diseases. In this study, we have evaluated apoptosis inducing the potential of ten new hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid. Cancerous leukemia cells (HL-60) and non-malignant fibroblasts (Swiss 3T3) were incubated with test compounds for 24 h and morphologically evaluated. The changes in mitochondrial membrane potential (Delta psi m) and caspase-3 activity were used to confirm the results and to study early induction of apoptosis. Cytotoxicity was determined using the lactate dehydrogenase (LDH) assay and mutagenicity with miniaturized Ames-test. The most potent selective apoptosis inducers were compounds 1c and 1h having IC50 values of 41 and 23 mu M, respectively, in leukemia cells (HL-60) while effects in fibroblasts (Swiss 3T3) were insignificant. Reduction of 6 m and increase in caspase-3 activity were observed already during the first 2 hr in the HL-60 cells treated with compounds 1 c and 1 h. Neither of the compounds was cytotoxic or mutagenic. The results indicate that compounds 1 c and 1 h are selective apoptosis inducers and should be studied further for possible use in cancer therapy. Drug Dev. Res. 69: 185-195, 2008. (C) 2008 Wiley-Liss, Inc.",
keywords = "317 Pharmacy",
author = "Anna Galkin and Anu Surakka and {Boije af Genn{\"a}s}, Gustav and Timo Ruotsalainen and Kari Kreander and P{\"a}ivi Tammela and Kaarina Sivonen and Jari Yli-Kauhaluoma and Pia Vuorela",
year = "2008",
doi = "10.1002/ddr.20116",
language = "English",
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pages = "185--195",
journal = "Drug Development Research",
issn = "0272-4391",
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}

Hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid that selectively induce apoptosis in leukemia cells but not in fibroblasts. / Galkin, Anna; Surakka, Anu; Boije af Gennäs, Gustav; Ruotsalainen, Timo; Kreander, Kari; Tammela, Päivi; Sivonen, Kaarina; Yli-Kauhaluoma, Jari; Vuorela, Pia.

In: Drug Development Research, Vol. 69, No. 4, 2008, p. 185-195.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid that selectively induce apoptosis in leukemia cells but not in fibroblasts

AU - Galkin, Anna

AU - Surakka, Anu

AU - Boije af Gennäs, Gustav

AU - Ruotsalainen, Timo

AU - Kreander, Kari

AU - Tammela, Päivi

AU - Sivonen, Kaarina

AU - Yli-Kauhaluoma, Jari

AU - Vuorela, Pia

PY - 2008

Y1 - 2008

N2 - New apoptosis modulating agents are widely sought, because failure in regulation of apoptosis is associated with many diseases. In this study, we have evaluated apoptosis inducing the potential of ten new hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid. Cancerous leukemia cells (HL-60) and non-malignant fibroblasts (Swiss 3T3) were incubated with test compounds for 24 h and morphologically evaluated. The changes in mitochondrial membrane potential (Delta psi m) and caspase-3 activity were used to confirm the results and to study early induction of apoptosis. Cytotoxicity was determined using the lactate dehydrogenase (LDH) assay and mutagenicity with miniaturized Ames-test. The most potent selective apoptosis inducers were compounds 1c and 1h having IC50 values of 41 and 23 mu M, respectively, in leukemia cells (HL-60) while effects in fibroblasts (Swiss 3T3) were insignificant. Reduction of 6 m and increase in caspase-3 activity were observed already during the first 2 hr in the HL-60 cells treated with compounds 1 c and 1 h. Neither of the compounds was cytotoxic or mutagenic. The results indicate that compounds 1 c and 1 h are selective apoptosis inducers and should be studied further for possible use in cancer therapy. Drug Dev. Res. 69: 185-195, 2008. (C) 2008 Wiley-Liss, Inc.

AB - New apoptosis modulating agents are widely sought, because failure in regulation of apoptosis is associated with many diseases. In this study, we have evaluated apoptosis inducing the potential of ten new hydrophobic derivatives of 5-(hydroxymethyl)isophthalic acid. Cancerous leukemia cells (HL-60) and non-malignant fibroblasts (Swiss 3T3) were incubated with test compounds for 24 h and morphologically evaluated. The changes in mitochondrial membrane potential (Delta psi m) and caspase-3 activity were used to confirm the results and to study early induction of apoptosis. Cytotoxicity was determined using the lactate dehydrogenase (LDH) assay and mutagenicity with miniaturized Ames-test. The most potent selective apoptosis inducers were compounds 1c and 1h having IC50 values of 41 and 23 mu M, respectively, in leukemia cells (HL-60) while effects in fibroblasts (Swiss 3T3) were insignificant. Reduction of 6 m and increase in caspase-3 activity were observed already during the first 2 hr in the HL-60 cells treated with compounds 1 c and 1 h. Neither of the compounds was cytotoxic or mutagenic. The results indicate that compounds 1 c and 1 h are selective apoptosis inducers and should be studied further for possible use in cancer therapy. Drug Dev. Res. 69: 185-195, 2008. (C) 2008 Wiley-Liss, Inc.

KW - 317 Pharmacy

U2 - 10.1002/ddr.20116

DO - 10.1002/ddr.20116

M3 - Article

VL - 69

SP - 185

EP - 195

JO - Drug Development Research

JF - Drug Development Research

SN - 0272-4391

IS - 4

ER -