RESUMEN
The present investigation was designed to determine molecular and cellular events involved in anticancer properties of lutein derived from marigold (Tagetes erecta) petals using Human cervical carcinoma (HeLa) cell lines. In vitro experiments demonstrated that lutein at concentration of 10⯵M significantly inhibited proliferation of HeLa cells by up to 62.85% after 24â¯h of treatment and 84.85% after 48â¯h of treatment. In addition, lutein inhibited proliferation of HeLa cells in a dose-dependent manner by inducing apoptosis. Lutein-treated HeLa cells also showed enhanced accumulation of reactive oxygen species (ROS) correlated with significant downregulation of Bcl-2 (anti-apoptotic) expression and upregulation of Bax (pro-apoptotic) expression. Furthermore, lutein mediated activation of caspase-3 and imbalance between Bax and Bcl-2 expression, causing significant loss of mitochondrial membrane potential of HeLa cells. TUNEL assays revealed significant damage of nuclei DNA in lutein-treated HeLa cells, demonstrating a critical role of lutein in the final stage of apoptosis. Taken together, the results indicate that lutein-induced apoptosis of HeLa cells occurs through enhanced ROS production, interaction with mitochondrial factors, and upregulation of caspase-3-mediated pathway, leading to fragmentation of nuclei DNA. Therefore, lutein could be potentially useful as a chemotherapeutic and/or chemopreventive biomolecule against Human cervical carcinoma.
Asunto(s)
Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Flores/química , Luteína/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Tagetes/química , Proteína X Asociada a bcl-2/metabolismo , Suplementos Dietéticos , Células HeLa , Humanos , Etiquetado Corte-Fin in Situ , Luteína/administración & dosificación , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
To develop Pleurotus eryngii varieties with improved medicinal qualities, protoplasts of P. eryngii were mutagenized using 4-nitroquinoleneoxide. The effects of the resulting variant mushrooms on a human cell were evaluated by applying their aqueous extracts to the human hepatoma cell line, HepG2, in vitro and examining any alteration in the proteomes of the treated HepG2. The P. eryngii mutant, NQ2A-12, was selected for its effects on increasing the expression level of Pin1 in HepG2. Pin1 is one of the peptidyl-prolyl cis-trans isomerases known to play an important role in repressing Alzheimer's disease pathogenesis. Validity of NQ2A-12 related to Alzheimer's disease was shown with an enhanced expression of Pin1 in a mouse brain tissue by injecting the NQ2A-12 extract. The mutant mushroom, NQ2A-12, could be developed as a new variety of P. eryngii with potential to protect against Alzheimer's disease.