Anesini C, Genaro A, Cremaschi G, Zubillaga M, Boccio J, Sterin-Borda L, Borda E
Departament of Pharmacology, Buenos Aires University, Argentina.
Acta Physiol Pharmacol Ther Latinoam. 1996;46(1):33-40.
We previously reported that aqueous extract of Larrea divaricata Cav. had an antiproliferative activity upon tumoral lymphoid cells (BW 5147), without affecting normal immunity. To determine the probable mechanism of the inhibitory action of the extract upon cell growth, the participation of intracellular signals involved in the inhibition of cell proliferation, namely the activation of adenylate cyclase system was studied. The production of cyclic 3', 5 adenosine monophosphate (cAMP) in presence and absence of extract was analized. The extract increased the cAMP levels, but neither the cAMP production nor the inhibitory effect of the extract on proliferation were blocked by a beta adrenergic receptor antagonist (propranolol) or by histaminergic receptor antagonists (cimetidine and mepyramine). So, we concluded that the antiproliferative activity of the extract of BW 5147 cells would be mediated by an increase in cAMP intracellular levels no related to the activation of the membrane receptors here studied. In parallel, the extract was administered to a pregnant rat with a spontaneous mammarian carcinoma and "in vivo" antitumoral activity was found.
我们之前报道过，拉瑞阿草（Larrea divaricata Cav.）的水提取物对肿瘤淋巴细胞（BW 5147）具有抗增殖活性，且不影响正常免疫功能。为了确定该提取物抑制细胞生长的可能机制，我们研究了参与细胞增殖抑制的细胞内信号，即腺苷酸环化酶系统的激活情况。分析了在有提取物和无提取物存在时环磷腺苷（cAMP）的产生情况。提取物可提高cAMP水平，但β肾上腺素能受体拮抗剂（普萘洛尔）或组胺能受体拮抗剂（西咪替丁和甲氧苄二胺）均不能阻断cAMP的产生，也不能阻断提取物对增殖的抑制作用。因此，我们得出结论，BW 5147细胞提取物的抗增殖活性是由细胞内cAMP水平升高介导的，这与本文所研究的膜受体激活无关。同时，将该提取物给予患有自发性乳腺癌的怀孕大鼠，并发现了其“体内”抗肿瘤活性。
