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Effect of caffeic acid and caffeic acid phenethyl ester on murine osteosarcoma cells: regulation of the NADPH oxidase complex

Grant number: 18/10321-2
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2019
Effective date (End): November 30, 2020
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Rodrigo Cardoso de Oliveira
Grantee:Ana Lígia Pagnan
Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Deregulation of normal cell mechanisms leads to the development of neoplastic processes, some of these processes are related to resistance to cellular apoptosis, proliferation signaling of the tumor mass, induction of angiogenesis, capacity for tissue invasion and metastasis. Tumor cells are commonly exposed to stress conditions, environmental factors and deregulation in oxidative metabolism. Reactive Oxygen Species (ROS) behave as important regulators of cell signaling and can participate in several stages of tumor progression, such as proliferation, resistance to apoptosis, induction of angiogenesis, invasion and metastasis. Bone cancer represents the sixth most frequent cancer group in the world, responsible for approximately 6% of cases of cancers in children and adolescents and for about 1% of all cancers that affect the general population. Osteosarcoma is the most common primary malignant tumor of bone tissue. Downregulation of oxidative metabolism is highly involved, as is the expression of NADPH oxidases (NOXes) and the production of Reactive Oxygen Species, playing a key role in the behavior of cancer cells. Therefore, it is necessary studies proposing alternative antitumor therapies. Caffeic acid, a compound derived from secondary plant metabolism, and its derivative, caffeic acid phenethyl ester (CAPE) has been shown in several studies to possess antioxidant, anti-inflammatory, antibacterial and anticarcinogenic properties. One of the main consequences of EROS is its reaction with lipid cell membranes, causing its structural disorganization and loss of function. In this context, several studies demonstrated the antioxidant capacity of CAPE, neutralizing the action of these EROS, thus protecting the cell membrane, besides participating in the suppression of proliferation, survival and invasion of different types of cancer cells. In view of the points presented and the fact that there are no records in the literature on the effects of caffeic acid and caffeic acid phenethyl ester on osteosarcoma, this study aims to investigate their role as possible antiproliferative agents in osteosarcoma cells. In the present work, it will be evaluated the effect of Caffeic Acid and Caffeic Acid Phenethyl Ester on cytotoxicity, apoptosis, reactive oxygen species production, migratory capacity and proliferation, analysis of NOX genes by Real-Time qPCR techniques and the expression of proteins by the Western Blot technique.

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