Antitumour effects of metformin and curcumin in human papillomavirus positive and negative head and neck cancer cells

Abstract

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has significantly increased in recent decades due to human papillomavirus (HPV)‐mediated oncogenesis. Unfortunately, a growing number of HPV‐positive (+) OPSCC survivors are living with the irreversible side effects of treatment. The novel, well‐tolerated chemotherapeutics with improved side effect profiles are, therefore, in high demand. Metformin is one such drug, widely used as a first‐line oral agent in the treatment of type 2 diabetes mellitus. Curcumin is another well‐tolerated agent quickly gaining attention for its medicinal properties. Both metformin and curcumin have been shown to display anticancer properties. This study aimed to determine the antitumor effects of these agents, individually and combined, in HPV+​​​​ ​​​and HPV‐negative (−) head and neck squamous cell carcinoma (HNSCC) cell lines. This was achieved by assessing the efficacy of varying drug concentrations on the overall cell viability, proliferation, and expression of common HNSCC biomarkers. The results from protein and RNA expression data are highly variable, as expected, with multiple pathways being affected in cancer. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays and immunofluorescence microscopy suggest that both agents are capable of slowing proliferation and inducing apoptosis. We conclude that curcumin and metformin display effective antitumor effects in both HPV+ and HPV− HNSCC cell lines. The curcumin effects appear more pronounced in the HPV− cell lines. Metformin appears to be more effective at reducing the overall cell numbers in HPV+ cell lines. Metformin and curcumin combined did not appear to have synergistic effects on the proliferation or apoptosis of the treated cell lines.

Curcumol enhances the anti-tumor effects of metformin via suppressing epithelial-mesenchymal transition in triple-negative breast cancer

“…Metformin was reported to inhibit TNBC cell proliferation, colony formation and induce apoptosis through activating the intrinsic and extrinsic signaling pathways (15). The effects of metformin combined with curcumin, another active ingredient isolated from curcuma, on the progression of some tumors, including breast cancer, have been investigated (16)(17)(18). Structurally, however, curcumol and curcumin differ, which suggests that they might possess different bioactivity (19).…”

Usefulness of Melatonin and Other Compounds as Antioxidants and Epidrugs in the Treatment of Head and Neck Cancer

“…Curcumin is a yellow pigment isolated from the plant Curcuma longa. It exerts anti-inflammatory properties by inhibiting cyclooxygenases (COX) and other enzymes and blocks the formation of ROS; it also and disrupts cell signal transduction by various mechanisms, including inhibition of protein kinase C [ 127 , 128 ]. However, curcumin is an unstable compound with low bioavailability, which makes it necessary to explore approaches to counteract these weaknesses.…”

Investigation of potential antiviral natural products with an effect on HPV18 E6 protein by molecular docking method

“…This compound reduces the regulation of both serine kinase AKT/nuclear factor κB pathways by sensitizing cancer cells [16]. Curcumin also inhibits telomerase activity, the RAS and extracellular signal-regulated kinases (ERKs) signaling pathways, cyclin D1, cyclooxygenase 2, and nitric oxide synthase activity, and inhibits cell growth by reducing the expression of HPV oncoproteins [17][18][19].…”