Correlating Artepillin C cytotoxic activity on HEp-2 cells with bioinspired systems of plasma membranes

Autor(es)

Kobal, Mirella B. ^[1] ; Pazin, Wallance M. ^[2] ; Bistaffa, Maria J. ^[1] ; Constantino, Carlos J. L. ^[2] ; Toledo, Karina A. ^[1] ; Aoki, Pedro H. B. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Sci Humanities & Languages, BR-19806900 Assis, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Technol & Appl Sci, BR-19060900 Presidente Prudente, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Materials Science & Engineering C-Materials for Biological Applications; v. 112, JUL 2020.
• Citações Web of Science: 0

Resumo

Artepillin C is the main compound present in propolis from Baccharis dracunculifolia, whose antitumor activity has been the focus of many studies. Herein, we shall investigate the Artepillin C mechanisms of action against cells derived from the oropharyngeal carcinoma (HEp-2). Cytotoxicity tests revealed that the concentrations of Artepillin C required to reduce cell viability by 50% (CC50) are dependent on the incubation time, decreasing from 40.7 x 10(-5) mol/L to 15.7 x 10(-5) mol/L and 9.05 x 10(-5) mol/L considering 12, 24 and 48 h, respectively. Hydrophobic interactions on neutral species of Artepillin C induce aggregation over the HEp-2 plasma membrane, given the acid conditions of the cellular culture. Indeed, Langmuir monolayers mimicking cellular membranes of tumor cells revealed Artepillin C affinity to interact with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) containing 20 mol% of 1,2-dipalmitoyl-sn-glychero-3-phosphoserine (DPPS), leading aggregation on giant unilamellar vesicles (GUVs) at pH 3.2. Moreover, leakage experiments on GUVs have shown that the presence of DPPS enhances the efflux of the fluorescent probe signaling the membrane permeabilization, which is the origin of the necrotic pathway triggered in HEp-2 cells, as observed by flow cytometry assays. (AU)

• Processo FAPESP: 18/02392-7 - Ação do Artepillin C em cultivo de células derivadas do carcinoma de orofaringe (HEp-2)
• Beneficiário: Mirella Boaro Kobal
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 16/09633-4 - Mecanismo de ação do composto bioativo Artepillin C em sistemas miméticos de membranas e membranas citoplasmáticas de células tumorais
• Beneficiário: Wallance Moreira Pazin
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado