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

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...

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Main Authors: Sijia Sun, Ampai Phrutivorapongkul, Dya Fita Dibwe, Chandrasekar Balachandran, Suresh Awale
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/62574
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-625742018-11-29T07:55:57Z Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line Sijia Sun Ampai Phrutivorapongkul Dya Fita Dibwe Chandrasekar Balachandran Suresh Awale Biochemistry, Genetics and Molecular Biology Chemistry Medicine Pharmacology, Toxicology and Pharmaceutics 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. 2018-11-29T07:32:43Z 2018-11-29T07:32:43Z 2018-08-24 Journal 15206025 01633864 2-s2.0-85052553843 10.1021/acs.jnatprod.8b00405 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
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
Chemistry
Medicine
Pharmacology, Toxicology and Pharmaceutics
spellingShingle Biochemistry, Genetics and Molecular Biology
Chemistry
Medicine
Pharmacology, Toxicology and Pharmaceutics
Sijia Sun
Ampai Phrutivorapongkul
Dya Fita Dibwe
Chandrasekar Balachandran
Suresh Awale
Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line
description 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.
format Journal
author Sijia Sun
Ampai Phrutivorapongkul
Dya Fita Dibwe
Chandrasekar Balachandran
Suresh Awale
author_facet Sijia Sun
Ampai Phrutivorapongkul
Dya Fita Dibwe
Chandrasekar Balachandran
Suresh Awale
author_sort Sijia Sun
title Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line
title_short Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line
title_full Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line
title_fullStr Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line
title_full_unstemmed Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line
title_sort chemical constituents of thai citrus hystrix and their antiausterity activity against the panc-1 human pancreatic cancer cell line
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052553843&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/62574
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