Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line

• Main Authors: Sijia Sun, Ampai Phrutivorapongkul, Dya Fita Dibwe, Chandrasekar Balachandran, Suresh Awale
• Format: Journal
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Chemistry; Medicine; Pharmacology, Toxicology and Pharmaceutics
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052553843&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/62574
• Institution: Chiang Mai University

Copyright © 2018 American Chemical Society and American Society of Pharmacognosy. Human pancreatic cancer cells have an extreme tolerance to nutrition starvation, enabling them to survive in a hypovascular tumor microenvironment. Searching for agents that preferentially inhibit cancer cell viability under nutrition starvation conditions is a novel antiausterity strategy in anticancer drug discovery. In the present study, a hexane extract of the peels of Citrus hystrix fruits showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells using a nutrient-deprived medium. Phytochemical investigation of this bioactive extract led to the isolation of 10 coumarins (1-10) including a new furanocoumarin (1). The isolated compounds were tested for their preferential cytotoxic activity against three different human pancreatic cancer cell lines [PANC-1, MIA PaCa-2, and PSN-1]. Among these, bergamottin (7) was identified as the most active constituent. In real-time live imaging, 7 was found to induce cell shrinkage, membrane blebbing, and disintegration of organelles in PANC-1 cells. Bergamottin (7) was also found to inhibit PANC-1 cell migration and colony formation. Mechanistically, 7 inhibited key survival proteins in the Akt/mTOR signaling pathway. Bergamottin (7) and related compounds are potential antiausterity candidates for drug development against pancreatic cancer.