Related Experiment Video
Updated: Jun 19, 2026
Multiplexed Live-Cell Imaging for Drug Responses in Patient-Derived Organoid Models of Cancer
Published on: January 5, 2024
Suberoylanilide hydroxamic acid (SAHA) potentiates paclitaxel-induced apoptosis in ovarian cancer cell lines
Charles S Dietrich1, Victoria L Greenberg, Christopher P DeSimone
1Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Tripler Army Medical Center, 1 Jarrett White Road, Honolulu, HI 96859-5000, USA. chuck.dietrich@us.army.mil
Objectives:
To determine if SAHA, a histone deacetylase inhibitor, decreases ovarian cancer cell viability when combined with paclitaxel in vitro, and to explore molecular alterations of combined paclitaxel+SAHA treatment.
Methods:
SKOV3 and Hey ovarian cancer cell lines were treated for 24 h with paclitaxel, then re-treated with SAHA or paclitaxel for an additional 48 h. Protein extracts were prepared at 48 h for western blot analysis. Cell viability was assessed at 72 h using the ApoAlert Annexin V Apoptosis Kit.
Results:
SAHA causes G1 and G2 cell cycle arrest in ovarian cancer cell lines. Cell viability was significantly reduced by combined paclitaxel+SAHA treatment. In Hey cells, viability was reduced to 67% with paclitaxel, and to 48% with paclitaxel+SAHA (p<0.001). In the SKOV3 cell line, viability was reduced to 70% with continuous paclitaxel treatment, and was further reduced to 57% in the combined treatment group (p<0.05). Increased PARP cleavage was noted in the paclitaxel+SAHA groups. SAHA increased expression of p21cip1/waf1 and p27Kip1, down regulated cyclins A and B, and suppressed CDK1. Paclitaxel induced expression of survivin, an inhibitor of apoptosis protein, was reduced to baseline control levels with the addition of SAHA. The pro-apoptotic protein, Bad, was also increased with SAHA.
Conclusions:
Paclitaxel+SAHA reduces cell viability in excess of either agent alone in ovarian cancer cell lines. Cell death is mediated via several mechanisms including G1/G2 arrest from CDK1 downregulation, inhibition of paclitaxel-induced survivin accumulation, and from increased Bad expression.
Insights
The combination of SAHA and paclitaxel significantly reduces ovarian cancer cell viability more than either drug alone. This combined treatment induces cell death through cell cycle arrest and apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Ovarian cancer remains a leading cause of cancer-related deaths in women.
- Paclitaxel is a standard chemotherapy agent for ovarian cancer.
- Histone deacetylase inhibitors (SAHA) are being investigated for their anti-cancer properties.
Purpose of the Study:
- To evaluate the synergistic effect of SAHA and paclitaxel on ovarian cancer cell viability in vitro.
- To investigate the molecular mechanisms underlying the combined treatment's efficacy.
Main Methods:
- Ovarian cancer cell lines (SKOV3, Hey) were treated with paclitaxel and SAHA.
- Cell viability was assessed using Annexin V Apoptosis Kit.
- Protein expression and cell cycle alterations were analyzed via Western blot.
Main Results:
- Combined paclitaxel+SAHA significantly reduced ovarian cancer cell viability compared to single agents.
- The combination induced G1/G2 cell cycle arrest by downregulating CDK1 and increasing p21/p27.
- SAHA inhibited paclitaxel-induced survivin expression and increased pro-apoptotic Bad protein.
Conclusions:
- Paclitaxel and SAHA exhibit synergistic cytotoxicity against ovarian cancer cells.
- Mechanisms include cell cycle arrest, inhibition of survivin, and promotion of apoptosis.
- This combination therapy holds potential for ovarian cancer treatment.
