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 derivativ e hexadecylphosphocholine (miltefosine) is locally used to control skin met astases of breast cancer. Since intravesical chemotherapy represents a form of topical treatment we investigated whether a new APC with a long alkyl c hain would be active against 5637 and EJ bladder cancer cell lines. Their a ntineoplastic activity was inversely related to the alkyl chain length of t he respective APC. Erucylphosphocholine and its congener with modified phos phocholine head erucylphospho-N,N,N-trimethylpropanolamine were the most ef fective derivatives. APC with alkyl chains over 16 carbons in length induce d programmed cell death in both cell lines, as determined by oligonucleosom al DNA fragmentation and morphology. The distinct antineoplastic effects le ad us to predict that urinary bladder instillation of APC will be of therap eutic benefit for patients with urinary bladder neoplasia. (C) 1999 Elsevie r Science Ireland Ltd. All rights reserved.