Franzese O, Comandini A, Cannavò E, Pepponi R, Falcinelli S, Graziani G, Bonmassar E
Department of Neurosciences, University of Rome (Tor Vergata), Italy.
Melanoma Res. 1998 Aug;8(4):323-8. doi: 10.1097/00008390-199808000-00005.
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.
先前的研究表明，环戊烯酮前列腺素在多种小鼠和人类肿瘤模型中具有抗肿瘤活性。在本研究中，四种人类黑色素瘤细胞系在体外分别用不同浓度（4-16微克/毫升）的前列腺素A1（PGA1）处理24小时或48小时。处理结束时，测定细胞增殖（以DNA合成来衡量）和端粒酶活性。结果显示，在SK-MEL-28细胞中，PGA1在48小时时诱导了浓度依赖性的DNA合成抑制，但在24小时时未出现。相反，在PGA1处理仅24小时后就检测到端粒酶活性受到显著抑制。此外，在用该药物处理48小时后，端粒酶的抑制比细胞增殖的抑制更为明显。对三种新产生的黑色素瘤细胞系进行的进一步研究证实，PGA1能早期抑制细胞生长，并伴有端粒酶活性的显著受损。这些结果表明，基于两种不同机制，PGA1作为抗肿瘤药物可能具有潜在价值：对黑色素瘤细胞的直接细胞生长抑制/细胞毒性作用，以及对负责癌细胞永生的肿瘤相关酶功能（即端粒酶）的抑制活性。
