Inhibition of estradiol uptake and transforming growth factor alpha secretion in human breast cancer cell line MCF-7 by an alkyl-lysophospholipid.
We investigated the effect of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), an alkyl-lysophospholipid, on the uptake of estrogen, the secretion of transforming growth factor (TGF) alpha and the content of progesterone receptors (PRs) in the hormone-dependent breast cancer cell line, MCF-7. The uptake of labeled estradiol by MCF-7 was dose dependently decreased by 12 h pretreatment with 10-25 micrograms/ml ET-18-OCH3, and this suppression occurred prior to the onset of the inhibitory action of ET-18-OCH3 on MCF-7 growth. Scatchard analysis demonstrated that ET-18-OCH3 reduced the number of estrogen receptors in MCF-7 without affecting their affinity. Both the secretion of TGF-alpha from MCF-7 into the conditioned medium and the PR content of MCF-7 were decreased by 48 h treatment with 10 micrograms/ml ET-18-OCH3. The estradiol uptake, the TGF-alpha secretion, and the PR content were not affected by platelet-activating factor, lyso-PAF, and palmitoyl-lysophosphatidylcholine, all at 10 micrograms/ml. These results suggest that the reduction of estrogen receptor level induced by ET-18-OCH3 resulted in decreases in both the secretion of TGF-alpha and the content of PR in MCF-7, and these effects are specific to ET-18-OCH3. We concluded that these effects of ET-18-OCH3 may lead, at least partly, to its antitumor action in hormone-dependent breast cancer cell lines.
Kosano
H
H
Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Yasutomo
Y
Y
Kugai
N
N
Nagata
N
N
Inagaki
H
H
Tanaka
S
S
Takatani
O
O
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013997:Time Factors; D015291:Transforming Growth Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D011980:Receptors, Progesterone; C026659:edelfosine; D004958:Estradiol; D015291:Transforming Growth Factors