Goldin Natalia, Heyfets Alina, Reischer Dorit, Flescher Eliezer
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
J Bioenerg Biomembr. 2007 Feb;39(1):51-7. doi: 10.1007/s10863-006-9061-y.
Jasmonates are plant stress hormones that induce suppression of proliferation and death in cancer cells, while being selectively inactive towards non-transformed cells. Jasmonates can overcome apoptotic blocks and exert cytotoxic effects on drug-resistant cells expressing p53 mutations. Jasmonates induce a rapid depletion of ATP in cancer cells. Indeed, this steep drop occurs when no signs of cell death are detectable yet. Experiments using modulators of ATP synthesis via glycolysis or oxidative phosphorylation suggest that the latter is the pathway suppressed by jasmonates. Consequently, the direct effects of jasmonates on mitochondria were evaluated. Jasmonates induced cytochrome c release and swelling in mitochondria isolated from cancer cells but not from normal ones. Thus, the selectivity of jasmonates against cancer cells is rooted at the mitochondrial level, and probably exploits differences between mitochondria from normal versus cancer cells. These findings position jasmonates as promising anti-cancer drugs acting via energetic depletion in neoplastic cells.
茉莉酸酯是植物应激激素，可诱导癌细胞增殖抑制和死亡，同时对未转化细胞具有选择性无活性。茉莉酸酯可克服凋亡阻滞，并对表达p53突变的耐药细胞发挥细胞毒性作用。茉莉酸酯可导致癌细胞中ATP迅速耗竭。事实上，这种急剧下降发生在尚未检测到细胞死亡迹象之时。使用通过糖酵解或氧化磷酸化调节ATP合成的实验表明，后者是茉莉酸酯抑制的途径。因此，评估了茉莉酸酯对线粒体的直接影响。茉莉酸酯可诱导从癌细胞而非正常细胞分离的线粒体中细胞色素c释放和肿胀。因此，茉莉酸酯对癌细胞的选择性源于线粒体水平，可能利用了正常细胞与癌细胞线粒体之间的差异。这些发现将茉莉酸酯定位为有望通过肿瘤细胞能量耗竭发挥作用的抗癌药物。
