Diacetylcurcumin: a new photosensitizer for antimicrobial photodynamic therapy in Streptococcus mutans biofilms.

This study evaluated the effect of antimicrobial photodynamic therapy (aPDT) on S. mutans using diacetylcurcumin (DAC) and verified DAC toxicity. In vitro, S. mutans biofilms were exposed to curcumin (CUR) and DAC and were light-irradiated. Biofilms were collected, plated and incubated for colony counts. DAC and CUR toxicity assays were conducted with Human Gingival Fibroblast cells (HGF). In vivo, G. mellonella larvae were injected with S. mutans and treated with DAC, CUR and aPDT. The hemolymph was plated and incubated for colony counts. Significant reductions were observed when DAC and CUR alone were used and when aPDT was applied. HGF assays demonstrated no differences in cell viability for most groups. DAC and CUR reduced the S. mutans load in G. mellonella larvae both alone and with aPDT. Systematic toxicity assays on G. mellonella demonstrated no effect of DAC and CUR or aPDT on the survival curve.

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1.

Curcumin is a potential anticancer drug with poor bioavailability, which limits its clinical use as a therapeutic agent. The aim of this study was a preliminary evaluation of the curcumin analogue CH-5 as a cytotoxic agent in human osteosarcoma cell lines U2OS, MG-63, and Saos-2. CH-5 inhibited cell viability at lower concentrations than curcumin, leading to the induction of apoptosis. The cellular levels of the transcription factors p53 and Sp1 affect the expression of cellular pathways that lead to apoptosis. CH-5 increased p53 protein levels in U2OS cells and reduced Sp1 levels, with a consequent effect on the expression of their target genes DNA methyltransferase 1 (DNMT1) and growth arrest and DNA damage-inducible 45 alpha gene (Gadd45a). CH-5 repressed DNMT1 and increased Gadd45a mRNA expression, which was dependent on p53, as this effect was only observed in the colorectal cancer cell line HCT116 with active p53, but not in the isogenic p53-deficient HCT116 cells. CH-5 also reduced the protein levels of DNMT1, which led to the upregulation of Gadd45a. These results suggest that CH-5 has potentially higher anticancer activity than curcumin, which is associated with the expression of apoptosis-associated genes regulated by the transcription factors Sp1 and p53. Future work on CH-5 will define the therapeutic potential of this compound in vivo.

Curcumin Analog CH-5 Suppresses the Proliferation, Migration, and Invasion of the Human Gastric Cancer Cell Line HGC-27.

Gastric cancer is one of the most frequent malignant tumors in the world. The majority of patients are diagnosed with metastatic gastric cancer, which has a low survival rate. These data reinforce the importance of studying the anticancer activity of new molecules with the potential to suppress gastric cancer metastasis. Curcumin is a well-studied compound that has demonstrated anti-metastatic effects. Here we investigated if CH-5, a curcumin derivative compound, has anti-metastatic properties in the human gastric cancer cell line HGC-27. Firstly, we found that CH-5 decreased viability and induced apoptosis in HGC-27 cells in a dose-dependent manner. Additionally, CH-5 suppressed the migration and invasion of HGC-27 cells by downregulating the expression and collagenase activity of matrix metalloproteinase 2 in a dose-dependent manner. In conclusion, CH-5 showed anticancer activities, including the induction of apoptosis, and the suppression of migration and invasion in HGC-27 cells, suggesting that CH-5 can be a lead molecule for the development of anti-metastatic drugs for gastric cancer therapy.

Antibacterial activity of diacetylcurcumin against Staphylococcus aureus results in decreased biofilm and cellular adhesion.

PURPOSE: Staphylococcus aureus infections have contributed to the global healthcare burden, particularly with regard to hospital-acquired meticillin-resistant S. aureus (MRSA) infections. METHODOLOGY: This study describes the antibacterial activity of diacetylcurcumin (DAC) against meticillin-susceptible S. aureus/MRSA biofilm formation, survival, metabolic activity and structure; its ability to prevent bacterial adhesion to human cells; and toxicity in Galleria mellonella larvae. RESULTS: DAC showed excellent antibacterial activity, with MIC ranging between 17.3 and 34.6 µmol l-1, and minimum bactericidal concentration ranging between 69 and 277 µmol l-1. It significantly reduced bacterial biofilm survival - by 22-63 % (at MIC, 10×MIC or 100×MIC) as compared to the 25-42 % reduction by vancomycin (P<0.0001) - and severely affected biofilm cell structures, leading to damaged architecture and the formation of amorphous cell clusters. Treatment with DAC (MIC/4) decreased bacterial adhesion to HaCaT keratinocytes from 1 to 5 h (P<0.0001). Finally, DAC demonstrated low toxicity in G. mellonella at its effective anti-biofilm concentrations. CONCLUSION: These findings open new avenues for the study of this curcumin derivative as an excellent prototype with anti-MRSA activity.