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Timosaponin AIII inhibits gastric cancer growth by the promotion of programmed cell death via the activation of p300/acetyl-p53 and Akt/MEK/ERK signaling
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DOI：10.3389/fphar.2026.1821689.png)
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Abstract
En 中文
Gastric cancer (GC) is a common cancer and causes severe deaths worldwide; while the current treatment cannot meet its medical needs. Timosaponin AIII (Timo AIII) is an active component isolated from Anemarrhena asphodeloides Bunge; which is a well-known Chinese Materia Medica and has multiple pharmacological activities; particularly anti-cancer activities. In this study; zebrafish and human GC cell models are utilized for the evaluation of the anti-GC activity of Timo AIII by integrating bioinformatics analysis and classical pharmacological approaches. We found that Timo AIII significantly decreased the GC growth in zebrafish. In human GC cell BGC-823; Timo AIII suppressed the cell viability; proliferation and migration in concentration- and time-dependent manners. Timo AIII blocked cell-cycle progression and promoted cell apoptosis. Moreover; Timo AIII activated programmed cell death (PCD); including apoptosis; ferroptosis; necroptosis and autophagy. The pharmacological inhibition of these processes and PI3K/Akt/MAPKs signaling by their specific inhibitors could partially abolish the anti-GC effect of Timo AIII. For the mechanistic study; the bioinformatics analysis revealed that p53 might be the central downstream effector of Timo AIII; promoting PCD. Timo AIII increased the intracellular protein levels of MEK; acetyl-p53 and p300 and the phosphorylation levels of Akt and MEK in BGC-823 cells; while it decreased the protein levels of p53 and Akt and the phosphorylation levels of ERK. In conclusion; Timo AIII presents anti-GC activity and the underlying mechanism is likely to be the activation of PCD via p300/acetyl-p53 and Akt/MEK/ERK signaling.
Keywords:
zebrafish
programmed cell death
gastric cancer
p53
p300
timosaponin AIII
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