Synergistic Combination of Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid and Natural Flavonoid Curcumin Exhibits Anticancer and Antibacterial Activity

Abstract

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.

Antimicrobial Potential of Curcumin: Therapeutic Potential and Challenges to Clinical Applications

“…Curcumin was also co-delivered with suberoylanilide hydroxamic acid in order to improve its water solubility and efficacy. The results showed that such a synergistic combination displayed stronger antibacterial action for curcumin than suberoylanilide hydroxamic acid and pure curcumin alone [78].…”

Aflatoxin B1 Toxicity and Protective Effects of Curcumin: Molecular Mechanisms and Clinical Implications

“…), and pathogenic pathogens (e.g., Staphylococcus aureus , Enteropathogenic Escherichia coli , and Mycobacterium tuberculosis ) [ 54 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. Additionally, several clinical studies have shown that curcumin has a strong therapeutic potential for treating a few chronic illnesses, including pulmonary, cancer, neurological, cardiovascular, infectious, neoplastic, psychiatric, and metabolic disorders [ 68 ]. Not surprisingly, several in vitro and animal experimental studies confirmed that curcumin supplementation could offer strong protective effects against AFB1-induced liver injury, mutagenicity, hepatocarcinogenicity, renal dysfunction, ileum damage, immune toxicity via regulating multiple above-mentioned targets [ 26 , 34 , 60 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”

The Natural Product Curcumin as an Antibacterial Agent: Current Achievements and Problems

“…Importantly, human trials showed that oral administration of curcumin was safe and effective for skin diseases, including psoriasis, infection, acne, skin inflammation, and skin cancer [14]. Bacterial infections also contribute to tumor formation, and curcumin combinations with some drugs have both anti-cancer and antibacterial activities that would provide a novel thyroid cancer treatment strategy [15]. In the present review, we survey the literature on the antibacterial properties and current underlying molecular mechanism of curcumin per se, curcumin-based combinations, and its nanoformulations, clinical trials, and major challenges, aiming to provide a prospective into the further clinical application of this promising antimicrobial candidate or broad-spectrum antibacterial adjuvant.…”