γ- and δ-Tocotrienols interfere with senescence leading to decreased viability of cells

• Published in: Molecular and cellular biochemistry 2021-02, Vol.476 (2), p.897-908
• Main Authors: Janubova, Maria, Hatok, Jozef, Konarikova, Katarina, Zitnanova, Ingrid
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Autophagy - drug effects; Bioactive compounds; Biochemistry; Biomedical and Life Sciences; Cardiology; Caspase-3; Cell cycle; Cell morphology; Cell proliferation; Cell Survival - drug effects; Cell viability; Cells, Cultured; Cellular Senescence - drug effects; Chromans - pharmacology; Cytology; DNA fragmentation; Etoposide; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Galactosidase; Gene expression; Humans; Hydrogen peroxide; Life Sciences; Medical Biochemistry; Microtubule-Associated Proteins - metabolism; Morphology; Oncology; Proteins; Senescence; Vitamin E; Vitamin E - analogs & derivatives; Vitamin E - pharmacology; β-Galactosidase
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-020-03954-w

Senescence is an irreversible permanent cell cycle arrest accompanied by changes in cell morphology and physiology. Bioactive compounds including tocotrienols (vitamin E) can affect important biological functions. The aim of this study was to investigate how γ- and δ-tocotrienols can affect stress-induced premature senescence. We established two different models of premature stress senescence by induction of senescence with either hydrogen peroxide or etoposide in human lung fibroblasts MRC-5 (ECACC, England). We observed increased percentage of cells with increased SA-β-galactosidase activity, decreased cell viability/proliferation and increased level of p21 in both models. In addition, γ-tocotrienol or δ-tocotrienol (both at concentrations of 150, 200 and 300 μM) were added to the cells along with the inductor of senescence (cotreatment). We have found that this cotreatment led to the decrease of cell viability/proliferation in both models of premature stress senescence, but did not change the percentage of senescent cells. Moreover, we detected no expression of caspase-3 or apoptotic DNA fragmentation in any models of premature stress senescence after the cotreatment with γ- as well as δ-tocotrienols. However, an increased level of autophagic protein LC-3 II was detected in cells with hydrogen peroxide—induced senescence after the cotreatment with γ-tocotrienol as well as δ-tocotrienol. In case of etoposide—induced senescence only δ-tocotrienol cotreatment led to an increased level of LC-3 II protein in cells. According to our work δ-tocotrienol is more effective compound than γ-tocotrienol. Graphic abstract