Discovery of potential antiausterity agents from the Japanese cypress Chamaecyparis obtusa. Issue 21 (1st November 2017)

• Record Type: Journal Article
• Authors: Dibwe, Dya Fita; Sun, Sijia; Ueda, Jun-ya; Balachandran, Chandrasekar; Matsumoto, Kinzo; Awale, Suresh
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 21(2017)
• Page Start: 4898
• Page End: 4903
• Publication Date: 2017-11-01
• Subjects: Pancreatic cancer -- Antiausterity agents -- Chamaecyparis obtusa -- PANC-1 -- Autophagy; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.09.034
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.