Cancer cells adapted to the microenvironment in tumor such as hypoxic and nutrient-starved conditions are now paid much attention as the therapeutic target of cancer. In the course of search for selective cytotoxic substances against cancer cells adapted to nutrient starvation, xanthone derivative of secalonic acid D (1) was isolated from culture extract of marine-derived Penicillium oxalicum. Compound 1 showed cytotoxic activity on the human pancreatic carcinoma PANC-1 cells adapted to glucose-starved conditions with IC₅₀ value of 0.6 µM, whereas IC₅₀ value of compound 1 against PANC-1 cells under general culture conditions was calculated to be more than 1000 µM. Further study indicated that compound 1 inhibited the Akt signaling pathway under glucose-starved conditions, and slightly affected the induction of glucose-regulated protein 78 (GRP78), and these effects would be mediated by the uncoupling action of compound 1 on the mitochondria.

中文翻译：

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二十烷酸D作为癌细胞上的一种选择性细胞毒性物质，适合营养不足。

作为癌症的治疗目标，适应缺氧和营养缺乏的肿瘤等微环境的癌细胞现在受到了广泛的关注。在寻找适合于营养饥饿的癌细胞的选择性细胞毒性物质的过程中，从海洋来源的草酸青霉的培养物提取物中分离出了secalonic acid D（1）的x吨酮衍生物。化合物1对人胰腺癌PANC-1细胞显示出细胞毒性活性，该细胞适应葡萄糖缺乏条件，IC ₅₀值为0.6 µM，而化合物1的IC ₅₀值为在一般培养条件下，针对PANC-1细胞的抗性被计算为大于1000 µM。进一步的研究表明，化合物1在葡萄糖缺乏的条件下抑制Akt信号传导途径，并稍微影响葡萄糖调节蛋白78（GRP78）的诱导，这些作用将由化合物1对线粒体的解偶联作用来介导。