Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2017-09-15 , DOI: 10.1016/j.bmcl.2017.09.034 Dya Fita Dibwe , Sijia Sun , Jun-ya Ueda , Chandrasekar Balachandran , Kinzo Matsumoto , Suresh Awale
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.
中文翻译:
从日本柏Chamaecyparis obtusa中发现潜在的抗紧缩剂
发现日本柏Chamaecyparis obtusa的氯仿提取物优先在营养缺乏的培养基中杀死PANC-1人胰腺癌细胞,而在营养丰富的条件下不会引起毒性。在此提取物导致了新的倍半萜烯(的隔离植物化学物质调查1),与六倍半萜(一起2 - 7)和木脂素(8)。通过使用抗衰老策略,测试了分离出的化合物对五种不同的人类胰腺癌细胞系[PANC-1,MIA PaCa2,CAPAN-1,PSN-1和KLM-1]的优先细胞毒性活性。其中,α-cadinol(2)被确定为最活跃的成分。α-卡丁醇(2)被发现抑制Akt / mTOR途径的活化,并且自噬的过度活化导致营养物饥饿期间优先的PANC-1细胞死亡。