Potential of Curcumin-Quercetin Loaded Nanostructured Lipid Carriers as Oral Squamous Cell Carcinoma Adjuvant Therapy by Downregulating AKT/PI3K Signaling Pathway

Abstract

Introduction: Oral squamous cell carcinoma (OSCC) is an oral epithelial neoplasm with worldwide prevalence of 95% among all oral malignancies. Therapy of OSCC include radiation, chemotherapy, and surgery but causes subsequent cell death, ineffective long-term therapy, and infection risk at surgical site. Curcumin-quercetin is flavonoid derived from Curcuma longa and Allium cepa that can induce apoptosis and inhibit cells metastasis. Combination of curcumin-quercetin has low solubility hence encapsulated by nanoparticle is necessary. Nanostructured lipid carriers (NLCs) can enhance loading capacity and improve stability of curcumin-quercetin, biocompatible, and enhance site-specific targeting efficiency. Administration of combination of curcumin-quercetin loaded nanostructured lipid carrier by injection targeting OSCC cell. Purpose: To analyze the potency of curcumin-quercetin loaded NLCs as OSCC therapy by downregulating AKT/PI3K signaling pathway. Discussion: Curcumin-quercetin loaded NLCs are injected into the body then reach the target cells. This combination later would be encapsulated releasing curcumin-quercetin. Curcumin-quercetin suppresses the AKT/PI3K signaling pathway which is considered as strong cell cycle inductor, inhibitor of pro-apoptotic proteins expression, and has a pivotal role in OSCC metastasis. Inhibition of the pathway decreases the expression of cyclin A/D/E and manifests in the G1/G2/M phase arrest. This condition accompanied by p53 and FOXO-1 expression leads to apoptosis. Downregulating of this pathway decreases NF-kB expression then the expression of MMP-2/9 is lowered and manifests in inhibition of extracellular matrix degradation. This condition leads to migration and metastasis inhibition. Conclusion: Curcumin-quercetin loaded NLCs is potential for OSCC therapy by downregulating AKT/PI3K signalling pathway.