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SAHA Enhances Cisplatin-Induced Apoptosis in Oral Squamous Cell Carcinoma

Strategic Insights

— 1 min read

Researchers at Tohoku University in Sendai, Japan, have discovered that the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), significantly enhances the efficacy of cisplatin (CDDP) in inducing apoptosis in oral squamous cell carcinoma (OSCC) cells. The study, published in Cancer Chemotherapy and Pharmacology, found that SAHA potently induces apoptosis in OSCC cells by activating endoplasmic reticulum (ER) stress, which leads to the up-regulation of specific-ER stress-associated events.

Key Takeaways:

  • SAHA, a histone deacetylase inhibitor, enhances the efficacy of cisplatin (CDDP) in inducing apoptosis in oral squamous cell carcinoma (OSCC) cells.
  • The study found that SAHA potently induces apoptosis in OSCC cells by activating endoplasmic reticulum (ER) stress, which leads to the up-regulation of specific-ER stress-associated events.
  • SAHA alone rapidly induces sustained phosphorylation of eukaryotic translation initiation factor-2 (eIF2)alpha, which is up-regulated during ER stress.
  • Inhibition of ER stress by salubrinal, an inhibitor of eIF2 alpha dephosphorylation, abrogated SAHA's enhancement of CDDP cytotoxicity.
  • Levels of phospho-Akt are decreased in SAHA-treated cells, and this is in turn associated with increased activity of protein phosphatase 1 (PP1) by SAHA, the phosphatase upstream of Akt.
  • The study concluded that up-regulation of specific-ER stress-associated events is an integral part of the mechanism by which SAHA enhances CDDP-induced apoptosis.

Statistics:

  • 60% of HSC-3 cells became apoptotic after 48 h of treatment with CDDP/SAHA.
  • SAHA alone rapidly induced sustained phosphorylation of eIF2 alpha in OSCC cells.
  • SAHA's enhancement of CDDP cytotoxicity was abrogated by inhibition of ER stress by salubrinal.

Sources:

  • Suzuki, M., et al. (2009). Enhancement of cisplatin cytotoxicity by SAHA involves endoplasmic reticulum stress-mediated apoptosis in oral squamous cell carcinoma cells. Cancer Chemotherapy and Pharmacology, 64(6), 1115-1122.
  • Tohoku University, Dept. of Microbiology & Immunology, Graduate School Dental, Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan.
  • Springer, 233 Spring St., New York, NY 10013, USA.

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