Recently, we have reported the induction of apoptosis by 2-amino-4-(3-nitrophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-NC) in HepG2, T47D and HCT116 cells with low nano molar IC50 values. In this study, anti-proliferative effects of modified 4-aryle-4H-chromenes derivatives; 2-amino-4-(3-bromophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-BC), 2-amino-4-(3-trifluoromethylphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-TFC) and 2-amino-4-(4,5-methylenedioxyphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (4, 5-MC) were investigated in three human cancer cell lines. Compared to 3-NC none of the compounds displayed better anti-proliferative effect, although 3-BC appeared somewhat similar. Therefore 3-NC was selected for further studies. Treatment of HepG2, T47D and HCT116 cells with this compound induced apoptosis as visualized by fluorescence microscopic study of Hoechst 33258 stained cells. Induction of apoptosis was quantified by Annexin V/PI staining using flow cytometry. Western blot analysis also revealed that 3-NC down-regulated the expression of anti-apoptotic protein Bcl2 and up-regulated pro-apoptotic protein Bax, in all of the cell lines. Nonetheless, HepG2 cell line was the most responsive to 3-NC as Bax and Bcl2 showed the most dramatic up and down regulation. Our previous finding that 3-NC down regulates Inhibitor of Apoptosis Proteins (IAPs) and the present observation that Bax is upregulated and Bcl2 is down regulated upon 3-NC treatment, this chromene derivative has the potential to overcome chemotherapy resistance caused by up regulation of these proteins.

Neuronal loss is one of the striking causes of various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features and clinical manifestations, they share some common mechanisms of disease pathology. Progressive regional loss of neurons in patients is responsible for motor, memory, and cognitive dysfunctions, leading to disabilities and death. Neuronal cell death in neurodegenerative diseases is linked to various pathways and conditions. Protein misfolding and aggregation, mitochondrial dysfunction, generation of reactive oxygen species (ROS), and activation of the innate immune response are the most critical hallmarks of most common neurodegenerative diseases. Thus, endoplasmic reticulum (ER) stress, oxidative stress, and neuroinflammation are the major pathological factors of neuronal cell death. Even though the exact mechanisms are not fully discovered, the notable role of mentioned factors in neuronal loss is well known. On this basis, researchers have been prompted to investigate the neuroprotective effects of targeting underlying pathways to determine a promising therapeutic approach to disease treatment. This review provides an overview of the role of ER stress, oxidative stress, and neuroinflammation in neuronal cell death, mainly discussing the neuroprotective effects of targeting pathways or molecules involved in these pathological factors.

Farnesiferol C is one of the major compounds, isolated from Ferula asafoetida (a type of coumarins) and used for cancer treatment as a folk remedy. Treatment of many cancers depends on oxidative stress situation. In this study, we sought the hypothesis that oxidative stress induced by Farnesiferol C contribute to anticancer property and induce apoptosis in MCF-7, human breast cancer cell line. We investigated the effect of Farnesiferol C on oxidative stress by measurement of some enzymes activity including catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), as well as some parameters such as total thiol and ROS levels. Also we evaluated Farnesiferol C effects on the cell cycle and apoptosis induction by using flow cytometry analysis. Our findings demonstrated that Farnesiferol C significantly induced apoptosis mediated by increasing in the cellular ROS levels. This compound increased cellular SOD and CAT activities in 24 and 48 h and reduced activity of these enzymes after 72 h exposure. Furthermore, MDA and total thiol levels were increased and decreased, respectively in the cells treated with Farnesiferol C after 24-72 h. G0/G1 phase cell cycle arrest followed by induction of apoptosis was also observed in MCF-7 cells after treatment with Farnesiferol C. According to these data, Farnesiferol C has a therapeutic effect on MCF-7 cells and can be suitable candidate for breast cancer treatment; however it is necessary for further experiments.