Combinatorial Effects of Curcumin with an Anti-Neoplastic Agent on Head and Neck Squamous Cell Carcinoma (HNSCC) Through the Regulation of EGFR -ERK1/2 and Apoptotic Signaling Pathways.
ACS Comb Sci. 2015 Oct 27. Epub 2015 Oct 27. PMID: 26505786
Globally, head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and represents about 6% of all diagnosed cancers. Use of anti-cancer drugs such as docetaxel, doxorubicin (DOX), 5-fluorouracil (5-FU), and cisplatin (diammine dichloroplatinum (II) (CDDP) is limited due to their non-specificity, drug resistance and toxicity. A combinatorial approach may improve the efficacy of these chemotherapeutic drugs and reduce their non-specific toxicities. In the present study, curcumin, an anti-cancer phytochemical was used in combination with 5-FU, doxorubicin and cisplatin and their combinatorial effect on HNSCC cell line, NT8e was investigated. Our results showed that the combination of 5-FU or DOX with curcumin exhibited significant growth inhibition and enhanced apoptosis in NT8e cancer cell lines. Treatment with 5-FU or DOX in combination with curcumin induced apoptosis by inhibiting Bcl-2 and increasing Bax, Caspase-3, and poly ADP ribose polymerase (PARP) in NT8e cells. This was further confirmed through apoptotic characteristic features in cells such as membrane blebbing, nuclear condensation and cell shrinkage observed by DAPI staining and through decreased red/green fluorescence by JC-1. These two combinations also exhibited cell cycle growth arrest at G1/S phase, which was confirmed by down-regulation of cyclins (D1, E2, B1 and A2), CDK2 and increased p21 levels. In addition, curcumin exposure along with 5-FU or DOX inhibited cell proliferation through the down-regulation of EGFR-ERK1/2 signaling molecules. Overall, our data demonstrates the promising therapeutic potential and underlying mechanisms of curcumin with 5-FU/ DOX combinations as a new treatment modality for head and neck cancer management.