Takigawa M, Tajima K, Fukuo K, Fujiki H, Suzuki F
J Biochem. 1987 Feb;101(2):397-404. doi: 10.1093/oxfordjournals.jbchem.a121924.
12-O-Tetradecanoylphorbol-13-acetate (TPA), a skin tumor-promoting phorbol ester, and teleocidin and aplysiatoxin, which are potent tumor promoters in mouse skin but are chemically unrelated to phorbol esters, induced change of cultured rabbit costal chondrocytes from a polygonal to a fibroblastic shape and inhibited glycosaminoglycan (GAG) synthesis and metachromatic matrix formation in these cells. The potencies of teleocidin and aplysiatoxin to inhibit GAG synthesis were almost the same as that of TPA. On the other hand, Tween 60 and cantharidin, weak mouse skin tumor promoters, phenobarbital, a liver tumor promoter, and saccharin, a bladder tumor promoter, had no effect on the morphology or GAG synthesis of cultured chondrocytes. Like TPA, teleocidin and aplysiatoxin increased DNA and RNA syntheses of chondrocytes. Parathyroid hormone (PTH) and dibutyryl cyclic AMP reversed the morphological and histochemical changes caused by a 4-day treatment with teleocidin or aplysiatoxin as well as with TPA, reversal being apparent after 2 days. PTH increased intracellular cyclic AMP after 2 min in chondrocytes pretreated with teleocidin or aplysiatoxin as well as with TPA. PTH also increased ornithine decarboxylase [ODC; EC 4.1.1.17] activity in these chondrocytes after 4 h. These results show that retention of responsiveness to PTH is a typical characteristic of chondrocytes dedifferentiated by treatment with TPA-type tumor promoters such as TPA, teleocidin and aplysiatoxin. The results also suggest that ODC induction mediated by elevation of cyclic AMP plays an important role in re-differentiation of teleocidin- and aplysiatoxin-treated chondrocytes.
12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）是一种促进皮肤肿瘤的佛波酯，以及在小鼠皮肤中具有强大肿瘤促进作用但与佛波酯化学结构无关的远侧素和海兔毒素，它们可使培养的兔肋软骨细胞从多边形变为成纤维细胞形状，并抑制这些细胞中糖胺聚糖（GAG）的合成和异染性基质形成。远侧素和海兔毒素抑制GAG合成的效力与TPA几乎相同。另一方面，吐温60和斑蝥素（弱的小鼠皮肤肿瘤促进剂）、苯巴比妥（一种肝脏肿瘤促进剂）以及糖精（一种膀胱肿瘤促进剂）对培养软骨细胞的形态或GAG合成没有影响。与TPA一样，远侧素和海兔毒素可增加软骨细胞的DNA和RNA合成。甲状旁腺激素（PTH）和二丁酰环磷腺苷可逆转远侧素或海兔毒素以及TPA处理4天后引起的形态和组织化学变化，2天后这种逆转明显。在用远侧素或海兔毒素以及TPA预处理的软骨细胞中，PTH在2分钟后可增加细胞内环磷腺苷水平。4小时后，PTH还可增加这些软骨细胞中鸟氨酸脱羧酶[ODC；EC 4.1.1.17]的活性。这些结果表明，对PTH保持反应性是经TPA、远侧素和海兔毒素等TPA类肿瘤促进剂处理后去分化的软骨细胞的典型特征。结果还表明，由环磷腺苷升高介导的ODC诱导在远侧素和海兔毒素处理的软骨细胞再分化中起重要作用。
