Identification of phosphofructokinase-1 as a target of Chinese olive fruit (Canarium album L.) extract in colorectal cancer cells: Mechanistic insights into cellular energy stress-induced apoptosis
Journal
Journal of Agriculture and Food Research
Journal Volume
26
Start Page
102684
ISSN
2666-1543
Date Issued
2026-03
Author(s)
Abstract
Colorectal cancer (CRC) is a significant cause of global cancer mortality. While conventional chemotherapeutics or single-agent compounds can suppress tumor growth, their dose-limiting toxicities often erode patient survival and quality of life. Plant extracts offer a distinct therapeutic advantage, leveraging multi-targeted pathways with inherently lower toxicity profiles. Here, we report the multi-signal transduction pathway of Chinese olive extract (COE) mediated CRC apoptosis. COE selectively inhibits CRC cell growth, with GI50 values significantly lower than in normal intestinal epithelial cells. Quantitative proteomics revealed COE-driven perturbations in cell cycle regulation, apoptosis, and metabolic reprogramming. Thermal proteome profiling and cellular thermal shift assay identified phosphofructokinase-1 (PFK1), a key glycolytic enzyme, as a direct molecular target of COE. Interrogation of The Cancer Genome Atlas data revealed that elevated PFK1 expression was linked to poorer CRC patient survival. Mechanistic studies demonstrated that COE suppresses PFK1 enzymatic activity, leading to cellular energy stress and activation of the adenosine monophosphate-activated protein kinase (AMPK)/p53 axis to promote apoptosis. Notably, amentoflavone, a biflavonoid constituent of COE, was computationally predicted and experimentally validated to inhibit PFK1, recapitulating COE's anti-proliferative effect. Collectively, our findings reveal that, besides regulating cell cycle and apoptosis, COE activates a previously unrecognized PFK1–AMPK/p53 signaling pathway, providing a mechanistic rationale for its development as a metabolism-oriented therapeutic strategy in CRC.
Subjects
Amentoflavone
Apoptosis
Colorectal cancer
Energy stress
Phosphofructokinase
Proteomics
Publisher
Elsevier BV
Description
Article number 102684
Type
journal article