Human urinary bladder carcinoma cell lines respond to treatment with alkylphosphocholines.
Alkylphosphocholines (APC) constitute a new group of antineoplastic agents without haematological toxicity. Their first clinically available derivative hexadecylphosphocholine (miltefosine) is locally used to control skin metastases of breast cancer. Since intravesical chemotherapy represents a form of topical treatment we investigated whether a new APC with a long alkyl chain would be active against 5637 and EJ bladder cancer cell lines. Their antineoplastic activity was inversely related to the alkyl chain length of the respective APC. Erucylphosphocholine and its congener with modified phosphocholine head erucylphospho-N,N,N-trimethylpropanolamine were the most effective derivatives. APC with alkyl chains over 16 carbons in length induced programmed cell death in both cell lines, as determined by oligonucleosomal DNA fragmentation and morphology. The distinct antineoplastic effects lead us to predict that urinary bladder instillation of APC will be of therapeutic benefit for patients with urinary bladder neoplasia.
Konstantinov
S M
SM
Unit of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Berger
M R
MR
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy*; D004249:DNA Damage; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006657:Histones; D009363:Neoplasm Proteins; D010767:Phosphorylcholine; C075010:erucylphosphocholine