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Antineoplastic activity of conjugates of lipids and 1‐β‐d‐arabinofuranosylcytosine
Author(s) -
Berdel Wolfgang E.,
Danhauser Susanne,
Schick Hans D.,
Hong Chung,
West Charles R.,
Fromm Michael,
Fink Ulrich,
Reichen Anneliese,
Rastetter Johann
Publication year - 1987
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02535560
Subject(s) - in vivo , cytotoxicity , chemistry , lewis lung carcinoma , in vitro , pharmacology , trypan blue , phosphocholine , cytotoxic t cell , conjugate , biochemistry , phospholipid , cancer , metastasis , phosphatidylcholine , biology , medicine , membrane , mathematical analysis , microbiology and biotechnology , mathematics
Five different lipid conjugates of 1‐β‐D‐arabinofuranosylcytosine (ARA‐C) were tested in comparison with ARA‐C, the ether lipid ET‐18‐OCH 3 (1‐ O ‐octadecyl‐2‐ O ‐methyl‐ rac ‐glycero‐3‐phosphocholine) and their equimolar mixtures. The compounds were tested in vitro for cytotoxicity in the trypan blue dye exclusion test with cells from six different leukemias, one glioblastoma and two bronchogenic carcinomas of human origin. The compounds were given in vivo to assess their therapeutic activity against 3‐Lewis lung carcinoma (3‐LL) of syngeneic C 57 Bl 6 mice. Although some of the conjugates have shown cytotoxic activity in vitro against the cell samples tested, they have not revealed higher cytotoxicity than ET‐18‐OCH 3 , ARA‐C or their equimolar mixtures. In these experiments, ARA‐CDP‐D,L‐MBA was the conjugate with the highest cytotoxicity. Some of the conjugates significantly inhibited tumor growth and also increased survival of C 57 Bl 6 mice with intraperitoneally (ip) implanted 3‐LL. In these experiments, ARA‐CDP‐D,L‐PTBA, ARA‐CDP‐D,L‐PBA, ARA‐CDP‐L‐dipalmitin and ARA‐CDP‐D,L‐PCA were more active than either the parent compounds ARA‐C and ET‐18‐OCH 3 alone or their equimolar mixtures. Furthermore, when the conjugates were injected as adjuvant chemotherapy shortly after the surgical removal of the primary 3‐LL, they inhibited the metastasis of 3‐LL to the lungs of the animals, demonstrated by an increase of the survival time and the number of surviving animals. The mode of action of these new antineoplastic compounds still is speculative.