1. GDP Induces PANC-1 Human Pancreatic Cancer Cell Death Preferentially under Nutrient Starvation by Inhibiting PI3K/Akt/mTOR/Autophagy Signaling Pathway.
- Author
-
Sun S, Kim MJ, Omar AM, Duy Phan N, Aoike M, and Awale S
- Subjects
- Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic isolation & purification, Cell Death drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Humans, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction drug effects, TOR Serine-Threonine Kinases metabolism, Antineoplastic Agents, Phytogenic pharmacology, Autophagy drug effects, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt antagonists & inhibitors, TOR Serine-Threonine Kinases antagonists & inhibitors
- 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 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., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)
- Published
- 2021
- Full Text
- View/download PDF