Fisher P B, Miranda A F, Mufson R A, Weinstein L S, Fujiki H, Sugimura T, Weinstein I B
Cancer Res. 1982 Jul;42(7):2829-35.
The potent tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) and related diterpene phorbol esters have been shown to enhance viral transformation and anchorage-independent growth, inhibit differentiation, and stimulate phosphatidylcholine turnover in various cell culture systems. In the present study, we report that teleocidin, and indole alkaloid isolated from Streptomyces, induces several biological effects similar to those of TPA in cell culture. Both TPA and teleocidin enhanced transformation of a clone of Fischer rat embryo cells (CREF) by a temperature-sensitive mutant of adenovirus type 5 (H5ts125); enhanced the cloning efficiency in agar of E11 cells, a clone of H5ts125-transformed Sprague-Dawley rat embryo cells; inhibited melanogenesis in murine B-16 melanoma cells; inhibited myogenesis in myoblast cultures established from normal human skeletal muscle; and stimulated choline release from prelabeled phospholipids of C3H10T 1/2 mouse cells. In general, TPA and teleocidin were equipotent in inducing these biological effects and were most active in the 3- to 10-ng/ml range, i.e., approximately 10(-8) to 10(-9) M. These studies provide further evidence that teleocidin represents a new class of tumor-promoting agents with properties similar to, if not identical with, those of the phorbol ester tumor promoters. These findings also suggest that cell culture systems can be used to identify new types of tumor-promoting agents in addition to the diterpene phorbol esters.
强效肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）及相关的二萜佛波酯已被证明在各种细胞培养系统中可增强病毒转化和不依赖贴壁生长、抑制分化并刺激磷脂酰胆碱周转。在本研究中，我们报告了从链霉菌中分离出的吲哚生物碱远藤菌素在细胞培养中可诱导几种与TPA类似的生物学效应。TPA和远藤菌素均可增强5型腺病毒温度敏感突变体（H5ts125）对Fischer大鼠胚胎细胞克隆（CREF）的转化；提高E11细胞（H5ts125转化的Sprague - Dawley大鼠胚胎细胞克隆）在琼脂中的克隆效率；抑制小鼠B - 16黑色素瘤细胞的黑色素生成；抑制从正常人骨骼肌建立的成肌细胞培养中的肌生成；并刺激C3H10T 1/2小鼠细胞预先标记的磷脂中的胆碱释放。一般来说，TPA和远藤菌素在诱导这些生物学效应方面效力相当，在3至10 ng/ml范围内最为活跃，即大约10^(-8)至10^(-9) M。这些研究进一步证明远藤菌素代表了一类新的肿瘤促进剂，其性质与佛波酯肿瘤促进剂相似，即便不完全相同。这些发现还表明，除了二萜佛波酯外，细胞培养系统可用于鉴定新型肿瘤促进剂。
