Abstract
Objectives:
Curcumin has shown anti-proliferative effects in multiple cancers and is an inhibitor of NF-kB. Downstream curcumin inhibits various genes which play an important role in tumor growth and metastasis. However, curcumin’s effects are greatly diminished due to its poor solubility. This study compared the effect of curcumin against more soluble curcumin analogues on the cell proliferation and gene expression in head and neck cancer (HNC) cell lines.
Methods:
Two novel curcumin analogues were synthesized, 1-flouro-curcumin (CF1) and 2-flouro-curcumin (CF2), which have shown increased solubility compared to curcumin. Our lab developed three HNC cell lines: 351GFP, 351GFP G1, and 351GFP G2. 351GFP G1 and 351GFP G2 are more metastatic HNC cell lines. The effect of CF1 and CF2 was tested in these three cell lines on the cell growth and the inhibition of genes (IL8, MMP7, COX2, and epidermal growth factor receptor [EGFR]) which are important in growth and metastasis of HNC.
Results:
The IC50s of curcumin, CF1, and CF2 in the 351GFP G1 cell line are 7.38microM, 0.33microM, and 0.1microM, respectively. Curcumin analogues were 20-80 times more potent than curcumin. Western Blot analysis showed that curcumin analogues blocked expression of IL8, MMP7, COX2, and EGFR. The analogues also showed several fold greater inhibition of these genes compared to curcumin in the HNC cell lines.
Conclusions:
Both curcumin analogues show greater anti-proliferative effect than curcumin, inhibiting cell proliferation and expression of genes involved in HNC growth and metastasis. Because of their increased activity, curcumin analogues may be of potential benefit in future HNC therapies.
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