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Anticancer Activity of 2,3'-Dihydroxy-5'-Methoxystilbene Against NSCLC Cell Lines Through AKT-Dependent Mechanisms: A

Phisit Pouyfung1,2, Nonthalert Lertnitikul3,4, Noriyoshi Ogino5

  • 1Department of Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand.

International Journal of Molecular Sciences
|January 28, 2026
PubMed

Insights

A novel stilbene compound shows potent anticancer effects against non-small cell lung cancer (NSCLC) cells, with reduced toxicity to normal cells. This AKT-targeting agent demonstrates potential for new lung cancer therapies.

Area of Science:

  • Oncology
  • Molecular Pharmacology
  • Biochemistry

Background:

  • Non-small cell lung cancer (NSCLC) therapy resistance necessitates novel therapeutic agents.
  • Stilbenes are being investigated for their anticancer properties.

Purpose of the Study:

  • To evaluate the anticancer activity and selectivity of 2,3'-dihydroxy-5'-methoxystilbene in NSCLC.
  • To investigate the compound's mechanism of action, focusing on AKT signaling.
  • To assess the compound's potential for chemosensitization in combination therapy.

Main Methods:

  • In vitro assays using NSCLC cell lines (A549, H23, H460) and normal fibroblasts (NIH/3T3).
  • Cell viability, proliferation, colony formation, and migration assays.
  • Western blotting for AKT pathway proteins (p-AKT, p-GSK3β).
  • Molecular modeling and combination therapy studies with cisplatin.

Main Results:

  • 2,3'-dihydroxy-5'-methoxystilbene demonstrated significant cytotoxicity against NSCLC cells (IC50 values 23-24 μM for H23/H460) with low toxicity to normal fibroblasts (IC50 > 100 μM).
  • The compound inhibited proliferation, colony formation, and migration in a dose-dependent manner, inducing apoptosis.
  • Mechanistic studies revealed AKT-dependent activity via decreased p-AKT and p-GSK3β levels.
  • Synergistic effects with cisplatin were observed in A549 and H460 cells, but antagonism in H23 cells.

Conclusions:

  • 2,3'-dihydroxy-5'-methoxystilbene is a selective AKT-targeting stilbene with promising anticancer activity against NSCLC.
  • The compound exhibits context-dependent chemosensitizing effects, suggesting potential for combination therapies.
  • Further investigation into this compound could lead to novel therapeutic strategies for NSCLC.
Keywords:
2,3′-dihydroxy-5′-methoxystilbeneAKT/GSK3β signaling pathwaycell apoptosischemosensitizationnon-small cell lung cancer (NSCLC)

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