期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 27, 期 21, 页码 4898-4903出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2017.09.034
关键词
Pancreatic cancer; Antiausterity agents; Chamaecyparis obtusa; PANC-1; Autophagy
资金
- Toyama Daichi Ginko Foundation
- Takeda Science Foundation (TSF) fellowship
- Japan Society for the Promotion of Science (JSPS) [JP16K08319]
- Grants-in-Aid for Scientific Research [16K08319] Funding Source: KAKEN
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, a-cadinol (2) was identified as the most active constituent. alpha-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. (C) 2017 Elsevier Ltd. All rights reserved.
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