Suberoylanilide hydroxamic acid sensitizes human oral cancer cells to TRAIL-induced apoptosis through increase DR5

Cheng-Chang Yeh1, Yi-Ting Deng, De-Yuan Sha

  • 1School of Dentistry, National Taiwan University Medical Center, Taipei, Taiwan.

Insights

Suberoylanilide hydroxamic acid induces apoptosis in oral cancer cells, primarily via the DR5/TRAIL pathway. This compound also sensitizes resistant cells to TRAIL, suggesting a novel therapeutic approach for oral cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Suberoylanilide hydroxamic acid (SAHA) is a promising chemotherapeutic agent inducing tumor apoptosis.
  • SAHA exhibits synergistic anticancer activity with other treatments like radiation and TRAIL.
  • Its effects on human oral cancer cells warrant further investigation.

Purpose of the Study:

  • To investigate the mechanism of SAHA-induced apoptosis in human oral cancer cells.
  • To determine if SAHA can sensitize TRAIL-resistant oral cancer cells to TRAIL therapy.
  • To explore the potential of combined SAHA and TRAIL treatment for oral cancer.

Main Methods:

  • Western blotting to analyze protein expression (Fas, Fas ligand, DR4, DR5) and caspase activation.
  • Use of caspase inhibitors (Z-IETD-FMK, Z-LEHD-FMK) to elucidate apoptosis pathways.
  • Treatment of oral cancer cells (SAS, Ca9-22) with SAHA and recombinant TRAIL.

Main Results:

  • SAHA increased Fas, Fas ligand, DR4, and DR5 protein expression, activating caspase-8 and caspase-9.
  • Apoptosis was primarily mediated by the DR5/TRAIL pathway, as indicated by inhibition studies.
  • SAHA sensitized TRAIL-resistant oral cancer cells to TRAIL-induced apoptosis in a p53-independent manner.

Conclusions:

  • SAHA induces apoptosis in human oral cancer cells mainly through the DR5/TRAIL pathway.
  • SAHA can overcome TRAIL resistance in oral cancer cells.
  • Combined SAHA and TRAIL therapy presents a promising new treatment strategy for oral cancer.