Sensitivity of leukemia cell lines to cytotoxic alkyl-lysophospholipids in relation to O-alkyl cleavage enzyme activities.

Abstract

The human leukemia cell lines K562, HL60, and Raji and the mouse leukemia cell line L1210 showed a differential susceptibility to the action of the alkyl-lysophospholipid (ALP) 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3). After 48 hours, the 50% growth-inhibition doses (ID50) of ET-18-OCH3 were found to be 0.78 microgram/ml (HL60), 1.53 microgram/ml (Raji), 4.41 micrograms/ml (K562), and 5.05 micrograms/ml (L1210), as determined by [3H]thymidine incorporation. At the same time, cell viability was determined by trypan blue exclusion and revealed median lethal doses (LD50) of 3.5 micrograms/ml (HL60), 15 micrograms/ml (Raji), 24 micrograms/ml (L1210), and 38 micrograms/ml (K562). Since O-alkyl cleavage enzyme previously was suggested as being important in the detoxification of cytotoxic ALPs, the enzyme activity was compared with the susceptibility to ET-18-OCH3 in the distinct cell lines. In comparison to an approximate sevenfold to elevenfold (ID50 and LD50, respectively) difference in the susceptibility of the above leukemia cell lines to ET-18-OCH3, no significant difference in the specific activities (0.13-0.21 nmol/min/mg) of the O-alkyl cleavage enzyme was found in the above leukemia cell lines. Therefore, the differential sensitivity of the above lines investigated cannot be explained by differences in O-alkyl cleavage enzyme activity. Experiments with radiolabeled ET-18-OCH3 in Raji cells suggest, rather, a critical role for phospholipases C and/or D in ALP metabolism.

• Authors: C Unger, H Eibl, D J Kim, E A Fleer, J Kötting, H H Bartsch, G A Nagel, K Pfizenmaier
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 78 Issue 2 Pg. 219-22 (Feb 1987) ISSN: 0027-8874 [Print] United States
• PMID: 3468284 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Lysophosphatidylcholines
• Phosphatidylcholines
• Phospholipid Ethers
• Phospholipids
• edelfosine
• Hydrolases
• O-alkyl cleavage enzyme

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Division (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Humans
• Hydrolases (metabolism)
• Leukemia (enzymology)
• Leukemia L1210 (enzymology)
• Lysophosphatidylcholines (pharmacology)
• Mice
• Phosphatidylcholines (metabolism)
• Phospholipid Ethers
• Phospholipids (metabolism)