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Synergistic enhancement of the antiproliferative activity of cis ‐diamminedichloroplatinum(II) by the ether lipid analogue BM41440, an inhibitor of protein kinase C
Author(s) -
Hofmann Johann,
Ueberall Florian,
Posch Lydia,
Maly Karl,
Herrmann Dieter B. J.,
Grunicke Hans
Publication year - 1989
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/bf02535169
Subject(s) - phospholipid , phosphocholine , protein kinase a , protein kinase c , biochemistry , chemistry , kinase , phosphorylation , protein phosphorylation , biology , phosphatidylcholine , membrane
The new phospholipid analogue 3‐hexadecylmercapto‐2‐methoxy‐methyl‐propyl‐1‐phosphocholine inhibits the phospholipid‐calcium‐dependent protein kinase, partially purified from Walker carcinoma cells with a K i value of 0.56 μM. The compound inhibits the phorbol ester stimulated phosphorylation of the ribosomal protein S6 indicating that the depression of Ca 2+ ‐phospholipid‐dependent protein kinase by the alkyl phospholipid also occurs in intact cells. The dose effect curve for the inhibition of cell proliferation by 3‐hexadecylmercapto‐2‐methoxy‐methyl‐propyl‐1‐phosphocholine in Walker cells exhibits a close correlation to the dose effect curve for the depression of Ca 2+ ‐phospholipid‐dependent protein kinase activity. Although alternative mechanisms cannot be excluded, the data suggest that the growth inhibitory activity of 3‐hexadecylmercapto‐2‐methoxy‐methyl‐propyl‐1‐phosphocholine correlates with the inhibition of Ca 2+ ‐phospholipid‐dependent protein kinase. The antiproliferative activity of 3‐hexadecylmercapto‐2‐methoxymethyl‐propyl‐1‐phosphocholine is synergistically enhanced by cis ‐diamminedichloroplatinum(II).