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

Abstract

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.

Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2

“…Three replications were performed, and the values obtained for the target gene expression were normalized to GAPDH. The values obtained for tested gene expression were analyzed by the relative gene expression 2 −ΔΔCT method in the program Origin 8.0, where −ΔΔCT = (CT target  − CT GAPDH ) unknown  − (CT target  − CT GAPDH ) calibrator 69.…”

Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review

“…More studies are needed to evaluate the mechanism of curcumin synergism based on the different classes of antibiotics. In addition to antibacterial action, curcumin also reverses the drug resistance when used in combination with other anticancer agents such as cisplatin, 5-fluorouracil, oxaliplatin, and doxorubicin in multiple types of cancer cells including breast [68], colon [69], head and neck [70], and ovary [71]. The curcumin may have acted on the target or pathway related to the development of drug resistance, hence restoring the killing effect of the drugs [72, 73].…”

Docosahexaenoic acid and disulfiram act in concert to kill cancer cells: a mutual enhancement of their anticancer actions

“…New drug combinations have been clinically and experimentally tested with the goal of improving cancer therapeutic efficacy and minimizing side-effects and drug resistance [1–4]. However, ideal combination therapies remain to be developed.…”