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ID: ALA4043254

Journal: Bioorg Med Chem Lett

Title: Discovery of potential antiausterity agents from the Japanese cypress Chamaecyparis obtusa.

Authors: Dibwe DF, Sun S, Ueda JY, Balachandran C, Matsumoto K, Awale S.

Abstract: 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.

CiteXplore: 28947153

DOI: 10.1016/j.bmcl.2017.09.034