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Inositol-C2-PAF acts as a biological response modifier and antagonizes cancer-relevant processes in mammary carcinoma cells.
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- Additional Information
- Source:
Publisher: Springer Country of Publication: Netherlands NLM ID: 101552938 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-3436 (Electronic) Linking ISSN: 22113428 NLM ISO Abbreviation: Cell Oncol (Dordr) Subsets: MEDLINE
- Publication Information:
Original Publication: Dordrecht : Springer
- Subject Terms:
- Abstract:
Purpose: Previous studies have identified alkyl-phospholipids as promising compounds for cancer therapy by targeting constituents of the cell membrane and different signaling pathways. We previously showed that the alkylphospholipid Inositol-C2-PAF inhibits the proliferation and migration of immortalized keratinocytes and the squamous carcinoma-derived cell line SCC-25. Here, we investigated the effect of this compound on growth and motility as well as its mode of action in mammary carcinoma-derived cell lines.
Methods: Using BrdU incorporation and haptotactic cell migration assays, we assessed the effects of Inositol-C2-PAF on MCF-7 and MBA-MB-231 cell proliferation and migration. The phosphorylation status of signaling molecules was investigated by Western blotting as well as indirect immunofluorescence analysis and capillary isoelectric focusing.
Results: We found that Inositol-C2-PAF inhibited the growth as well as the migration in MCF-7 and MBA-MB-231 cells. Furthermore, we found that this compound inhibited phosphorylation of the protein kinase Akt at serine residue 473, but had no impact on phosphorylation at threonine 308. Phosphorylation of other kinases, such as Erk1/2, FAK and Src, which are targeted by Inositol-C2-PAF in other cells, remained unaffected by the compound in the mammary carcinoma-derived cell lines tested. In MCF-7 cells, we found that IGF-1-induced growth, as well as phosphorylation of Akt S473 , mTOR and the tumor suppressor pRB, was inhibited in the presence of Inositol-C2-PAF. Moreover, we found that in these cells IGF-1 had no impact on migration and did not seem to be linked to full Akt activity. Therefore, MCF-7 cell migration appears to be inhibited by Ino-C2-PAF in an Akt-independent manner.
Conclusion: The antagonistic effects of Inositol-C2-PAF on cell migration and proliferation are indicative for its potential for breast cancer therapy, alone or in combination with other cytostatic drugs.
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- Contributed Indexing:
Keywords: Akt phosphorylation; Breast cancer; IGF-1; Inositol-C2-PAF; MCF-7; MDA-MB-231; Migration; Proliferation
- Accession Number:
0 (1-O-octadecyl-2-O-(2-inositolylethyl)-glycero-3-phosphatidylcholine)
0 (Antineoplastic Agents)
0 (IGF1 protein, human)
0 (Platelet Activating Factor)
4L6452S749 (Inositol)
67763-96-6 (Insulin-Like Growth Factor I)
- Publication Date:
Date Created: 20180727 Date Completed: 20181211 Latest Revision: 20181211
- Publication Date:
20221213
- Accession Number:
10.1007/s13402-018-0387-3
- Accession Number:
30047091
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