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Updated: Jun 10, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Combination of suberoylanilide hydroxamic acid and ritonavir is effective against renal cancer cells
Akinori Sato1, Takako Asano, Akio Horiguchi
1Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan. zenpaku@ndmc.ac.jp
Objectives:
To investigate the combined effect of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) and the protease inhibitor ritonavir on renal cancer cells.
Methods:
Renal cancer cells (769P, 786O, A498, ACHN, Caki-1) and renal proximal tubule epithelial cells were treated with SAHA (0-5 μM) with or without ritonavir (0-50 μM). Cell viability, clonogenecity, and changes in cell cycle were evaluated. The expression of acetylated histone, retinoblastoma protein (Rb), phosphorylated Rb, histone deacetylases, X-linked inhibitor of apoptosis, survivin, and active caspase 3 was assessed using Western blot analysis.
Results:
SAHA induced histone acetylation and Rb dephosphorylation and inhibited cell growth in a time- and dose-dependent manner. SAHA and ritonavir combined inhibited cell proliferation effectively and promoted histone acetylation and Rb dephosphorylation but only slightly affected renal proximal tubule epithelial cell survival. The combination induced the accumulation of the sub-G(1) fraction, decreased the expression of X-linked inhibitor of apoptosis and survivin, and increased active caspase 3, thus inducing apoptosis. It also inhibited the expression of histone deacetylases.
Conclusions:
Combination therapy using SAHA and ritonavir inhibited the proliferation of renal cancer cells effectively, perhaps by inhibiting both histone deacetylase function and expression. It might be a useful new regimen for treating renal cancer.
Insights
Combining suberoylanilide hydroxamic acid (SAHA) and ritonavir effectively inhibits renal cancer cell proliferation by inducing apoptosis. This combination therapy shows promise for treating kidney cancer with minimal impact on normal kidney cells.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Kidney cancer remains a significant health concern with limited treatment options.
- Histone deacetylase (HDAC) inhibitors and protease inhibitors are emerging as potential therapeutic agents.
Purpose of the Study:
- To evaluate the synergistic effect of SAHA and ritonavir on renal cancer cells.
- To investigate the underlying molecular mechanisms of this combination therapy.
Main Methods:
- Renal cancer cell lines and normal renal cells were treated with varying concentrations of SAHA and ritonavir.
- Cell viability, proliferation, cell cycle, and apoptosis markers were assessed.
- Protein expression levels of key molecules were analyzed via Western blot.
Main Results:
- SAHA alone induced histone acetylation and inhibited cell growth.
- The combination of SAHA and ritonavir significantly inhibited cancer cell proliferation and induced apoptosis.
- This combination demonstrated minimal toxicity to normal renal proximal tubule epithelial cells.
- The treatment led to decreased expression of X-linked inhibitor of apoptosis and survivin, and increased active caspase 3.
Conclusions:
- Combination therapy with SAHA and ritonavir is a potent strategy for inhibiting renal cancer cell proliferation.
- The observed effects are likely mediated by the inhibition of HDAC function and expression, leading to apoptosis.
- This regimen holds potential as a novel treatment for renal cancer.
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