Effect of prostaglandin A1 on proliferation and telomerase activity of human melanoma cells in vitro.
Previous studies have shown that cyclopentenone prostaglandins are endowed with antitumour activity in various murine and human tumour models. In the present investigation four human melanoma cell lines were treated with graded concentrations (4-16microg/ml) of prostaglandin A1 (PGA1) for 24 or 48 h in vitro. At the end of the treatment, cell proliferation (measured in terms of DNA synthesis) and telomerase activity were determined. The results showed that PGA1 induced concentration-dependent inhibition of DNA synthesis at 48 h but not at 24 h in SK-MEL-28 cells. In contrast, marked inhibition of telomerase activity was detected after only 24 h of PGA1 treatment. Moreover, after 48h of treatment with the agent, inhibition of telomerase was more pronounced than inhibition of cell proliferation. Additional studies performed with three freshly generated melanoma cell lines confirmed that PGA1 produced early inhibition of cell growth accompanied by marked impairment of telomerase activity. These results suggest that PGA1 could be of potential value as antitumour agent, on the basis of two distinct mechanisms: direct cytostatic/cytotoxic effects on melanoma cells, and inhibitory activity on a tumour-associated enzymatic function (i.e. telomerase) that is responsible for cancer cell immortality.
Franzese
O
O
Department of Neurosciences, University of Rome (Tor Vergata), Italy.
Comandini
A
A
Cannavò
E
E
Pepponi
R
R
Falcinelli
S
S
Graziani
G
G
Bonmassar
E
E
D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011454:Prostaglandins A / Q000008:administration & dosage / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D019098:Telomerase / Q000378:metabolism*
D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D011454:Prostaglandins A; D019098:Telomerase; C100573:prostaglandin A1