Methoxyeugenol regulates the p53/p21 pathway and suppresses human endometrial cancer cell proliferation
| Autor: | Bruna Pasqualotto Costa, Florencia María Barbé-Tuana, Lucas Kich Grun, Gisele Branchini, Krist Helen Antunes Fernandes, Géssica Luana Antunes, Marcella Tornquist Nassr, Fernanda Bordignon Nunes, Fernando Mendonça Diz, Jarbas Rodrigues de Oliveira |
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| Rok vydání: | 2020 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Flow cytometry 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Drug Discovery Eugenol medicine Humans MTT assay Cytotoxicity 030304 developmental biology Cell Proliferation Pharmacology chemistry.chemical_classification 0303 health sciences Reactive oxygen species medicine.diagnostic_test Cell growth Cancer medicine.disease Antineoplastic Agents Phytogenic Endometrial Neoplasms Mitochondria Gene Expression Regulation Neoplastic chemistry Apoptosis Cell culture 030220 oncology & carcinogenesis Cancer research Female Tumor Suppressor Protein p53 Reactive Oxygen Species Signal Transduction |
| Zdroj: | Journal of ethnopharmacology. 267 |
| ISSN: | 1872-7573 |
| Popis: | Ethnopharmacological relevance Plant-derived compounds are a reservoir of natural chemicals and can act as drug precursors or prototypes and pharmacological probes. Methoxyeugenol is a natural compound found in plant extracts, such as nutmeg (Myristica fragrans), and it presents anthelmintic, antimicrobial, anti-inflammatory activities. Recently, interest in the anticancer activity of plant extracts is increasing and the therapeutic activity of methoxyeugenol against cancer has not yet been explored. Aim of the study The present study aimed to evaluate the cancer-suppressive role and the molecular signaling pathways of methoxyeugenol in human endometrial cancer (Ishikawa) cell line. Materials and methods Proliferation, viability, and cell toxicity were assessed by direct counting, MTT assay, and LDH enzyme release assay, respectively. Antiproliferative effect were evaluated by nuclear morphological changes along with the cellular mechanisms of apoptosis and senescence by flow cytometry. The underlying molecular and cellular mechanisms were investigated by RT-qPCR, reactive oxygen species (ROS) levels, mitochondrial dysfunction, and proliferative capacity. Results and conclusions Methoxyeugenol treatment significantly inhibited the proliferation and viability of Ishikawa cells. Probably triggered by the higher ROS levels and mitochondrial dysfunction, the gene expression of p53 and p21 increased and the gene expression of CDK4/6 decreased in response to the methoxyeugenol treatment. The rise in nuclear size and acidic vesicular organelles corroborate with the initial senescence-inducing signals in Ishikawa cells treated with methoxyeugenol. The antiproliferative effect was not related to cytotoxicity and proved to effectively reduce the proliferative capacity of endometrial cancer cells even after treatment withdrawal. These results demonstrated that methoxyeugenol has a promising anticancer effect against endometrial cancer by rising ROS levels, triggering mitochondrial instability, and modulating cell signaling pathways leading to an inhibition of cell proliferation. |
| Databáze: | OpenAIRE |
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