Lutein derived from marigold (Tagetes erecta) petals triggers ROS generation and activates Bax and caspase-3 mediated apoptosis of human cervical carcinoma (HeLa) cells

Abstract

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 μM significantly inhibited proliferation of HeLa cells by up to 62.85% after 24 h of treatment and 84.85% after 48 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.