Abstract
Ether-linked glycerophospholipids (ether lipids, EL) are membrane-interactive drugs selectively cytotoxic toward neoplastic cells compared with normal cells. No conclusive explanation has yet been provided for this selectivity. We now present data indicating that the drug 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OMe) induces apoptosis, or programmed cell death, in human leukemic cells. Apoptotic death is induced selectively by ET-18-OMe in HL60 cells, which are sensitive to the drug's cytotoxic action, but not in the resistant K562 cell line. Enrichment of HL60 cells with cholesterol (HL60-CHOL cells) significantly protects the cells from the cytotoxic effect and from the induction of apoptosis by ET-18-OMe; the percent age of fragmented DNA is only 17% for HL60-CHOL, compared with 50% in native HL60 cells after exposure to 20 μm ET-18-OMe for 24hr. Our study provides a possible explanation for differences in sensitivity to EL among different cell types and illustrates an indirect interaction of EL with cellular DNA.
| Original language | English |
|---|---|
| Pages (from-to) | 124-130 |
| Number of pages | 7 |
| Journal | International Journal of Cancer |
| Volume | 53 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1993 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Induction of apoptosis in human leukemic cells by the ether lipid 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine. A possible basis for its selective action. / Diomede, L.; Colotta, F.; Piovani, B.; Re, F.; Modest, E. J.; Salmona, M.
In: International Journal of Cancer, Vol. 53, No. 1, 1993, p. 124-130.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of apoptosis in human leukemic cells by the ether lipid 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine. A possible basis for its selective action
AU - Diomede, L.
AU - Colotta, F.
AU - Piovani, B.
AU - Re, F.
AU - Modest, E. J.
AU - Salmona, M.
PY - 1993
Y1 - 1993
N2 - Ether-linked glycerophospholipids (ether lipids, EL) are membrane-interactive drugs selectively cytotoxic toward neoplastic cells compared with normal cells. No conclusive explanation has yet been provided for this selectivity. We now present data indicating that the drug 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OMe) induces apoptosis, or programmed cell death, in human leukemic cells. Apoptotic death is induced selectively by ET-18-OMe in HL60 cells, which are sensitive to the drug's cytotoxic action, but not in the resistant K562 cell line. Enrichment of HL60 cells with cholesterol (HL60-CHOL cells) significantly protects the cells from the cytotoxic effect and from the induction of apoptosis by ET-18-OMe; the percent age of fragmented DNA is only 17% for HL60-CHOL, compared with 50% in native HL60 cells after exposure to 20 μm ET-18-OMe for 24hr. Our study provides a possible explanation for differences in sensitivity to EL among different cell types and illustrates an indirect interaction of EL with cellular DNA.
AB - Ether-linked glycerophospholipids (ether lipids, EL) are membrane-interactive drugs selectively cytotoxic toward neoplastic cells compared with normal cells. No conclusive explanation has yet been provided for this selectivity. We now present data indicating that the drug 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OMe) induces apoptosis, or programmed cell death, in human leukemic cells. Apoptotic death is induced selectively by ET-18-OMe in HL60 cells, which are sensitive to the drug's cytotoxic action, but not in the resistant K562 cell line. Enrichment of HL60 cells with cholesterol (HL60-CHOL cells) significantly protects the cells from the cytotoxic effect and from the induction of apoptosis by ET-18-OMe; the percent age of fragmented DNA is only 17% for HL60-CHOL, compared with 50% in native HL60 cells after exposure to 20 μm ET-18-OMe for 24hr. Our study provides a possible explanation for differences in sensitivity to EL among different cell types and illustrates an indirect interaction of EL with cellular DNA.
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U2 - 10.1002/ijc.2910530123
DO - 10.1002/ijc.2910530123
M3 - Article
VL - 53
SP - 124
EP - 130
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 1
ER -