Piper longum Constituents Induce PANC-1 Human Pancreatic Cancer Cell Death under Nutrition Starvation |
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Authors: | Yuki Fujihashi Min Jo Kim Juthamart Maneenet Suresh Awale |
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Institution: | Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, Toyama, 930-0194 Japan |
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Abstract: | Pancreatic cancer is a highly aggressive form of cancer with a poor prognosis, partly due to ‘austerity’, a phenomenon of tolerance to nutrient deprivation and survival in its hypovascular tumor microenvironment. Anti-austerity agents which preferentially diminish the survival of cancer cells under nutrition starvation is regarded as new generation anti-cancer agents. This study investigated the potential of Piper longum constituents as anti-austerity agents. The ethanolic extract of Piper longum was found to have preferential cytotoxicity towards PANC-1 human pancreatic cancer cells in a nutrient-deprived medium (NDM). Further investigation led to the identification of pipernonaline ( 3 ) as the lead compound with the strongest anti-austerity activity, inducing cell death and inhibiting migration in a normal nutrient medium, as well as strongly inhibiting the Akt/mTOR/autophagy pathway. Therefore, pipernonaline ( 3 ) holds promise as a novel antiausterity agent for the treatment of pancreatic cancer. |
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Keywords: | Piper longum pancreatic cancer antiausterity agent PANC-1 pipernonaline |
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