ABSTRACT
Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which involve inhibiting molecular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential and cytokine, protein and gene expression were investigated in head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified morphology and inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in the G2/M and S phases. A decrease in cell migration was also observed, and there was decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IFN-γ and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anticancer effects on tumor cells by regulating signaling pathways associated with head and neck cancer.
Subject(s)
Alkaloids , Apoptosis , Benzodioxoles , Head and Neck Neoplasms , Inflammation , Piperidines , Polyunsaturated Alkamides , Signal Transduction , Polyunsaturated Alkamides/pharmacology , Benzodioxoles/pharmacology , Piperidines/pharmacology , Piperidines/therapeutic use , Alkaloids/pharmacology , Humans , Cell Line, Tumor , Signal Transduction/drug effects , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/genetics , Inflammation/metabolism , Inflammation/drug therapy , Inflammation/genetics , Apoptosis/drug effects , Cell Movement/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Cytokines/metabolism , Cell Survival/drug effects , Cell Proliferation/drug effectsABSTRACT
Cervical cancer is the fourth-most common type of cancer in the world that causes death in women. It is mainly caused by persistent infection by human papillomavirus (HPV) that triggers a chronic inflammatory process. Therefore, the use of anti-inflammatory drugs is a potential treatment option. The effects of piperine, an amino alkaloid derived from Piper nigrum, are poorly understood in cervical cancer inflammation, making it a target of research. This work aimed to investigate the antitumor effect of piperine on cervical cancer and to determine whether this effect is modulated by the cyclooxygenase 2 (PTGS2) pathway using in vitro model of cervical cancer (HeLa, SiHa, CaSki), and non-tumoral (HaCaT) cell lines. The results showed that piperine reduces in vitro parameters associated with neoplastic evolution such as proliferation, viability and migration by cell cycle arrest in the G1/G0 and G2/M phases, with subsequent induction of apoptosis. This action was modulated by downregulation of cyclooxygenase 2 (PTGS2) pathway, which in turn regulates the secretion of cytokines and the expression of mitogen-activated protein kinases (MAPKs), metalloproteinases (MMPs), and their antagonists (TIMPs). These findings indicate the phytotherapeutic potential of piperine as complementary treatment in cervical cancer.
ABSTRACT
The unbiased approaches of the last decade have enabled the collection of new data on the biology of annexin A1 (ANXA1) in a variety of scientific aspects, creating opportunities for new biomarkers and/or therapeutic purposes. ANXA1 is found in the plasma membrane, cytoplasm, and nucleus, being described at low levels in the nuclear and cytoplasmic compartments of placental cells related to gestational diabetic diseases, and its translocation from the cytoplasm to the nucleus has been associated with a response to DNA damage. The approaches presented here open pathways for reflection upon, and intrinsic clarification of, the modulating action of this protein in the response to genetic material damage, as well as its level of expression and cellular localization. The objective of this study is to arouse interest, with an emphasis on the mechanisms of nuclear translocation of ANXA1, which remain underexplored and may be beneficial in new inflammatory therapies.
Subject(s)
Annexin A1 , Annexin A1/metabolism , Cell Nucleus/metabolism , Cell Survival , Cytoplasm/metabolism , Female , Humans , Placenta/metabolism , PregnancyABSTRACT
The objective of the present study was to evaluate the action of the crude hydroalcoholic extract of Piper cubeba fruits and isolated lignans (cubebin, dihydrocubebin, ethylcubebin, hinokinin and methylcubebin) on head and neck cancer cells. We evaluated the influence of the Piper cubeba extract and isolated lignans (10, 50 e 100 µg/mL) for 4, 24, 48 and 72 h, in the larynx (Hep-2) and oral (SCC-25) squamous cell carcinoma cells and normal fibroblasts, on morphology, cell proliferation and migration, cytotoxicity, genotoxicity and gene and protein expression (PTGS2, PTGER3, PTGER4, MMP2, MMP9). The results showed that the P. cubeba extract and different lignans do not alter the cellular morphology, but decrease cell proliferation and migration, have low cytotoxic and genotoxic effects, probably due to the alteration of the expression of genes and proteins involved with inflammatory process. From these data, we can conclude that the lignans cubebin and methylcubebin had a greater effect on head and neck cancer cells in the antiproliferative, antimigratory and genotoxic action, and could be the target of the development of new therapies including possible new drugs as a therapeutic resource for the treatment of head and neck cancer due to its immense range of biological properties.