Claflin A J, Vesely D L, Hudson J L, Bagwell C B, Lehotay D C, Lo T M, Fletcher M A, Block N L, Levey G S
Proc Natl Acad Sci U S A. 1978 Feb;75(2):989-93. doi: 10.1073/pnas.75.2.989.
We have recently described the presence of a guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] inhibitor (GCI) in an aqueous extract of the balsam pear (Momordica charantia abbreviata). Because the guanylate cyclase-cyclic GMP system is though to be involved in cell growth, DNA and RNA synthesis, and possible malignant transformation, we examined the effect of the aqueous extract containing GCI on an undifferentiated adenocarcinoma of the rat prostate and concanavalin-A-stimulated [3H]thymidine incorporation into cultured splenic lymphocytes, a process thought to be mediated by cyclic GMP. The results demonstrate that the extract of the balsam pear blocks both the growth of the rat prostatic adencarcinoma in vitro and [3H]thymidine incorporation into DNA. DNA histograms from flow cytometry indicated that the extract containing GCI inhibited in the G2 + M phase of the cell cycle, a presumed locus of cyclic GMP effects. In addition, guanylate cyclase activity was significantly greater in the tumor than normal prostate tissue and was decreased by the extract containing GCI. Cyclic GMP levels in the tumor in culture wer also decreased by addition of the extract. It remains to be determined whether or not the anti-tumor agent and GCI are the same substance.
我们最近报道了在苦瓜(Momordica charantia abbreviata)水提取物中存在一种鸟苷酸环化酶[GTP焦磷酸裂解酶(环化),EC 4.6.1.2]抑制剂(GCI)。由于鸟苷酸环化酶 - 环磷酸鸟苷系统被认为参与细胞生长、DNA和RNA合成以及可能的恶性转化,我们研究了含有GCI的水提取物对大鼠前列腺未分化腺癌以及伴刀豆球蛋白A刺激的[3H]胸腺嘧啶核苷掺入培养的脾淋巴细胞的影响,这一过程被认为是由环磷酸鸟苷介导的。结果表明,苦瓜提取物既能阻断大鼠前列腺腺癌在体外的生长,又能抑制[3H]胸腺嘧啶核苷掺入DNA。流式细胞术的DNA直方图表明,含有GCI的提取物在细胞周期的G2 + M期产生抑制作用,这是环磷酸鸟苷发挥作用的一个假定位点。此外,肿瘤组织中的鸟苷酸环化酶活性显著高于正常前列腺组织,且含有GCI的提取物可使其降低。在培养的肿瘤组织中加入提取物后,环磷酸鸟苷水平也降低了。抗肿瘤剂和GCI是否为同一物质仍有待确定。