Piperine interacts with molecular targets by modulating inflammatory molecules in head and neck cancer cells

Introduction: Natural products have motivated humanity to discover new therapeutic agents for various diseases, especially cancer. Head and neck squamous cell carcinomas consist of a group of malignant neoplasms which affect the mucous lining in different anatomical regions of the upper aerodigestive tract, occupying sixth place in terms of new cases and deaths. In reference, piperine stands out for being a bioactive phenolic component isolated mainly from black pepper (Piper nigrum), which contain a multitude of biological properties such as: anti-inflammatory, immunomodulatory, antioxidant and anticancer. Objective: Investigate the cellular and molecular mechanisms relevant to the antitumor effect of piperine in modulating the inflammatory pathway in head and neck cancer cells. Methods: Laryngeal (HEp-2) and tongue (SCC-25) carcinoma cell lines were initially treated with piperine (150uM) for 24 hours. Then, the following tests were performed: gene expression (PTGS2, PTGER4, MMP2 and MMP9) by PCR quantitative, analysis of Interleukins 1 beta (IL-1β), 8 (IL-8) and Interferon-gamma (IF-y) by ELISA, and evaluation of ERK and p38 proteins by immunocytochemistry. Results: Piperine significantly reduced the gene expression levels of PTGS2, MMP2, MMP9 and PTGER4 in HEp-2 cells. The expression of PTGS2 and MMP2 genes was remarkably reduced in SCC-25 cells, however, MMP9 and PTGER4, were not differentially expressed in this lineage. Regarding the ELISA assay, we observed that the secretion of cytokines IL-8, IL-1β, IF-γ was significantly reduced after treatment with piperine in HEp-2 and SCC-25 cells. With respect to the immunocytochemistry test, we verified that piperine inhibited the expression of ERK and p38, indicating a significant reduction of these proteins compared to the control group in both cell lines studied. Conclusions: Our results indicate that the mechanism of action of piperine is attributed to its ability to interact with a broad spectrum of molecular targets, including inflammation-related genes (PTGS2, MMP2, MMP9 and PTGER4), inflammatory cytokines (IL-8, IL-1β, IF-γ) and kinases (ERK and p38). In particular, piperine acts directly on inflammation-promoting molecules due to its anti-inflammatory and anticancer properties, being a potential natural product for the treatment of head and neck cancer.