Background and Objective:
Curcumin is an effective anti-cancer agent used in thyroid cancer treatments.
However, its use in clinical applications is limited due to low solubility and bioavailability. In this study, a novel
combination strategy was applied by combining curcumin with suberoylanilide hydroxamic acid (SAHA) to increase both
bioavailability of curcumin and the efficiency of SAHA, which has limited efficiency when used alone.
Methods:
MTT assay was used to determine the cell viability of B-CPAP cells upon treatment with SAHA, curcumin and
their combinations. Synergistic interactions between two agents were analyzed by Calcusyn software. Apoptosis and cell
cycle assays were measured by flow cytometry. Expressions of apoptotic and cell cycle-related proteins (PARP,
P21/CDKN1A/WAF1, P27/KIP1) were examined by western blot analysis. Broth microdilution assay was performed to
determine minimum inhibitory concentration (MIC) values against S.aureus.
Results:
Based on MTT assay, IC50 values for SAHA and curcumin were determined as 0.91 μM and 20.97 μM,
respectively. The combination index CI value was determined as 0.891 in B-CPAP cells, which demonstrate synergistic
activity. The apoptotic effect was achieved by combination treatment (51.85%) on B-CPAP cells by using half of the dose
required for SAHA and curcumin alone. Combination treatment showed significant increase in percentage of B-CPAP
cells in S-phase due to the cell arrest. Cleaved-PARP, P21/CDKN1A/WAF1 and P27/KIP1 protein expressions were
upregulated. Curcumin was found to have better antimicrobial activity than SAHA as having a lower MIC value and
checkerboard synergy analysis revealed that, the two compounds co-operate synergistically for the in-vitro killing of S.
aureus.
Conclusion:
In the present study, synergistic combinations of SAHA and curcumin were shown to have both anticancer
and antibacterial activities that would provide a novel thyroid cancer treatment strategy.