Dibwe Dya Fita, Sun Sijia, Ueda Jun-Ya, Balachandran Chandrasekar, Matsumoto Kinzo, Awale Suresh
Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Bioorg Med Chem Lett. 2017 Nov 1;27(21):4898-4903. doi: 10.1016/j.bmcl.2017.09.034. Epub 2017 Sep 15.
The chloroform extract of the Japanese cypress Chamaecyparis obtusa was found to kill PANC-1 human pancreatic cancer cells preferentially in the nutrient-deprived medium without causing toxicity in the nutrient rich condition. Phytochemical investigation on this extract led to the isolation of a new sesquiterpene (1), together with the six sesquiterpenes (2-7) and a lignan (8). The isolated compounds were tested for their preferential cytotoxicity activity against five different human pancreatic cancer cell lines [PANC-1, MIA PaCa2, CAPAN-1, PSN-1, and KLM-1] by utilizing an antiausterity strategy. Among them, α-cadinol (2) was identified as the most active constituent. α-Cadinol (2) was found to inhibit the activation of Akt/mTOR pathway, and the hyperactivation of autophagy leading to preferential PANC-1 cell death during nutrient-starvation.
日本扁柏（Chamaecyparis obtusa）的氯仿提取物被发现能在营养缺乏的培养基中优先杀死PANC-1人胰腺癌细胞，而在营养丰富的条件下不会产生毒性。对该提取物进行植物化学研究，分离出一种新的倍半萜（1），以及六种倍半萜（2 - 7）和一种木脂素（8）。利用一种抗紧缩策略，对分离出的化合物针对五种不同的人胰腺癌细胞系[PANC-1、MIA PaCa2、CAPAN-1、PSN-1和KLM-1]进行了优先细胞毒性活性测试。其中，α-杜松醇（2）被确定为活性最强的成分。发现α-杜松醇（2）能抑制Akt/mTOR通路的激活以及自噬的过度激活，从而导致在营养饥饿期间PANC-1细胞优先死亡。
