GDP Induces PANC-1 Human Pancreatic Cancer Cell Death Preferentially under Nutrient Starvation by Inhibiting PI3K/Akt/mTOR/Autophagy Signaling Pathway.

Published on Jul 2, 2021in Chemistry & Biodiversity2.039
· DOI :10.1002/CBDV.202100389
Sijia Sun5
Estimated H-index: 5
(University of Toyama),
Min Jo Kim4
Estimated H-index: 4
(University of Toyama)
+ 3 AuthorsSuresh Awale38
Estimated H-index: 38
(University of Toyama)
Sources
Abstract
Pancreatic tumors are hypovascular, which leads to a poor nutrient supply to support the aggressively proliferating tumor cells. However, human pancreatic cancer cells have extreme resistance to nutrition starvation, which enables them to survive under severe metabolic stress conditions within the tumor microenvironment, a phenomenon known as "austerity" in cancer biology. Discovering agents which can preferentially inhibit the cancer cells' ability to tolerate starvation conditions represent a new generation of anticancer agents. In this study, geranyl-2,4-dihydroxy-6-phenethylbenzoate (GDP), isolated from Boesenbergia pandurata rhizomes, exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition starvation conditions. GDP also possessed PANC-1 cell migration and colony formation inhibitory activities under normal nutrient-rich conditions. Mechanistically, GDP inhibited PI3K/Akt/mTOR/autophagy survival signaling pathway, leading to selective PANC-1 cancer cell death under the nutrition starvation condition. Therefore, GDP is a promising anti-austerity agent for drug development against pancreatic cancer.
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