Ability of the non-phorbol ester-type tumor-promoter thapsigargin to mimic the stimulatory effects of 12-0-tetradecanoylphorbol-13-acetate on ornithine decarboxylase activity, hydroperoxide production, and macromolecule synthesis in mouse epidermis in viv
Ability of the non-phorbol ester-type tumor-promoter thapsigargin to mimic the stimulatory effects of 12-0-tetradecanoylphorbol-13-acetate on ornithine decarboxylase activity, hydroperoxide production, and macromolecule synthesis in mouse epidermis in viv
复制标题
非佛波酯型肿瘤促进剂毒胡萝卜素在体内模拟 12-0-十四烷酰佛波醇-13-乙酸酯对小鼠表皮鸟氨酸脱羧酶活性、氢过氧化物产生和大分子合成的刺激作用的能力
DOI：
10.1002/ijc.2910550626
复制
发表时间：
1993
影响因子：
6.4
通讯作者：
Perchellet,JP
中科院分区：
文献类型：
--
作者：
Perchellet,EM;Gali,HU;Gao,XM;Perchellet,JP
非-12-0-十四酰基佛波醇-13-乙酸酯（TPA）型肿瘤促进剂毒胡萝卜素（TG）的生化作用在小鼠表皮中进行了体内表征，该物质不与佛波醇酯受体结合，也不激活蛋白激酶C（PKC）或增加肌醇多磷酸。需要冷刮法来检测TG对鸟氨酸脱羧酶（ODC）活性的诱导，该反应远小于TPA引起的反应，并且具有不同的时程，TG预处理不会改变或引起TPA对ODC诱导的不应状态。但TG刺激氢过氧化物（HPx）的产生以及RNA、蛋白质和DNA的合成几乎与TPA一样多。此外，TG和TPA对DNA合成的顺序效应是相同的：在8小时的早期抑制，随后在16 - 32小时的最大刺激。TG刺激的HPx产生需要蛋白质合成和黄嘌呤氧化酶、磷脂酶A2和脂氧合酶活性，但不需要RNA和DNA合成以及环氧合酶和蛋白酶活性。HPx对TG的反应不受PKC激活剂prostratin的模拟，也不受prostratin或特异性PKC抑制剂预处理的抑制。然而，Ca 2 +-ATP酶抑制剂环匹阿尼酸和Ca 2+离子载体和弱ODC诱导剂A23187显著地模拟了HPx对TG和TPA的响应。由于已知TG和A23187与TPA相比分别是弱的和不完全的肿瘤促进剂，因此本研究结果表明，在没有主要ODC诱导的情况下，Ca 2+动员和TPA或非TPA型药物共同的HPx反应不足以实现肿瘤促进。
The biochemical effects of the non‐12‐0‐tetradecanoylphorbol‐13‐acetate (TPA)‐type tumor promoter thapsigargin (TG), which does not bind to the phorbol‐ester receptor, or activate protein kinase C (PKC) or increase inositol polyphosphates, were characterized in mouse epidermisin vivo. The cold scraping method is required to detect the induction of ornithine decarboxylase (ODC) activity by TG, a response much smaller than that caused by TPA and with a different time course, TG pre‐treatments do not alter or cause a refractory state against ODC induction by TPA. But TG stimulates hydroperoxide (HPx) production and RNA, protein, and DNA synthesis almost as much as TPA. Moreover, the sequential effects of TG and TPA on DNA synthesis are identical: early inhibition at 8 hr followed by maximal stimulation at 16‐32 hr. TG‐stimulated HPx production requires protein synthesis and xanthine oxidase, phospholipase A2, and lipoxygenase activities but not RNA and DNA synthesis, and cyclooxygenase and protease activities. The HPx response to TG is not mimicked by the PKC activator prostratin or inhibited by pre‐treatments with prostratin or specific PKC inhibitors. However, the Ca2+‐ATPase inhibitor cyclopiazonic acid and the Ca2+ionophore and weak ODC inducer A23187 mimic remarkably the HPx responses to TG and TPA. Since TG and A23187 are known to be, respectively, weak and incomplete tumor promoters as compared with TPA, the present results suggest that the HPx responses common to Ca2+‐mobilizing and TPA‐ or non‐TPA‐type agents are insufficient to achieve tumor promotion in the absence of major ODC induction.