Premium
GDP Induces PANC‐1 Human Pancreatic Cancer Cell Death Preferentially under Nutrient Starvation by Inhibiting PI3K/Akt/mTOR/Autophagy Signaling Pathway
Author(s) -
Sun Sijia,
Kim Min Jo,
Omar Ashraf M.,
Duy Phan Nguyen,
Aoike Mio,
Awale Suresh
Publication year - 2021
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.202100389
Subject(s) - autophagy , pi3k/akt/mtor pathway , pancreatic cancer , protein kinase b , chemistry , cancer cell , cancer research , programmed cell death , cancer , microbiology and biotechnology , signal transduction , biology , biochemistry , medicine , apoptosis
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 represents 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.