Combinatorial Effects of Curcumin with an Anti-Neoplastic Agent on Head and Neck Squamous Cell Carcinoma Through the Regulation of EGFR-ERK1/2 and Apoptotic Signaling Pathways.
Globally, head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and represents approximately 6% of all diagnosed cancers. The 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 the 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 cells. 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, as observed by DAPI staining and through decreased red/green fluorescence by JC-1. These two combinations also exhibited cell cycle growth arrest at the G1/S phase, which was confirmed by downregulation 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 downregulation 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.
Centre For Nanotechnology and Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University , Thanjavur-613 401, India.
Banudevi
B
Sivanantham
Centre For Nanotechnology and Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University , Thanjavur-613 401, India.
Swaminathan
S
Sethuraman
Centre For Nanotechnology and Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University , Thanjavur-613 401, India.
Uma Maheswari
UM
Krishnan
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck
D000970:Antineoplastic Agents; D004317:Doxorubicin; C512478:EGFR protein, human; D066246:ErbB Receptors; D003474:Curcumin; D002945:Cisplatin; D005472:Fluorouracil
EGFR signaling; apoptosis; combinational therapy; curcumin; oral cancer