The Polyphenols α -Mangostin and Nordihydroguaiaretic Acid Induce Oxidative Stress, Cell Cycle Arrest, and Apoptosis in a Cellular Model of Medulloblastoma

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 23; p. 7230
• Main Authors: Rojas-Ochoa, Alberto, Córdova, Emilio J, Carrillo-García, Adela, Lizano, Marcela, Pedraza-Chaverri, José, Patiño, Nelly, Cruz-Gregorio, Alfredo, Osnaya, Norma
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.11.2021; MDPI
• Subjects: Apoptosis; Apoptosis - drug effects; Brain tumors; cancer; Carbonyls; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell death; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Cerebellar Neoplasms - pathology; Cytotoxicity; Evaluation; Flow cytometry; Humans; Kinases; Masoprocol - pharmacology; Medulloblastoma; Medulloblastoma - pathology; Models, Biological; NDGA; Nordihydroguaiaretic acid; Oxidative stress; Oxidative Stress - drug effects; Pediatrics; Polyphenols; Polyphenols - pharmacology; Prostate cancer; Xanthones - pharmacology; α-mangostin; apoptosis; cancer; NDGA; α-mangostin; cell cycle; medulloblastoma
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26237230

Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols α-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of α-mangostin or NDGA for 24 h. The cell viability was analyzed using crystal violet and trypan blue dyes. Determination of the glutathione (GSH)/glutathione disulfide (GSSG) ratio and levels of carbonylated proteins was performed to evaluate the oxidative stress. Cell cycle progression and induction of cell death by fluorochrome-couple and TUNEL assays were evaluated using flow cytometry assays. Individual treatments with α-mangostin or NDGA decreased the viability of Daoy cells in a dose-dependent manner, inducing G2/M and S-G2/M cell cycle arrest, respectively. Both polyphenols induced cell death and increased oxidative stress. Very interestingly, α-mangostin showed more potent effects than NDGA. Our results indicate that α-mangostin and NDGA exert important cytostatic and cytotoxic effects in the Daoy cell line. These data highlight the potential usefulness of these compounds as an alternative strategy in medulloblastoma treatment.