Fangchinoline, an Extract of the Stephania tetrandra S. Moore Root, Promoted Oxidative Stress-induced DNA Damage and Apoptosis and Inhibited Akt Signaling in Jurkat T Cells.

Abstract

Fangchinoline (Fan) is extracted from traditional Chinese medicine (called Fangji), or the root of Stephania tetrandra Moore. Fangji is well-known in Chinese medical literature for treating rheumatic diseases. Sjogren's syndrome (SS) is a rheumatic disease whose progression can be mediated via CD4+ T cell infiltration. This study identifies the potential role of Fan in inducing apoptosis in Jurkat T cells. First, we explored the biological process (BP) associated with SS development by performing a gene ontology analysis of SS salivary gland-related mRNA microarray data. The effect of Fan on Jurkat cells was investigated by analyzing the viability, proliferation, apoptosis, reactive oxygen species (ROS) production, and DNA damage. Biological process analysis showed that T cells played a role in salivary gland lesions in patients with SS, indicating the significance of T cell inhibition in SS treatment. Viability assays revealed that the half-maximal inhibitory concentration of Fan was 2.49 μM in Jurkat T cells, while the proliferation assay revealed that Fan had an inhibitory effect on the proliferation of Jurkat T cells. The results of the apoptotic, ROS, agarose gel electrophoresis, and immunofluorescence assays showed that Fan induced oxidative stress-induced apoptosis and DNA damage in a dosedependent manner. These results indicate that Fan could significantly induce oxidative stress-induced apoptosis and DNA damage and inhibit the proliferation of Jurkat T cells. Moreover, Fan further enhanced the inhibitory effect on DNA damage and apoptosis by inhibiting the pro-survival Akt signal.