Baicalein induces cell death in murine T cell lymphoma via inhibition of thioredoxin system. (October 2017)

• Record Type: Journal Article
• Authors: Patwardhan, Raghavendra S.; Pal, Debojyoti; Checker, Rahul; Sharma, Deepak; Sandur, Santosh K.
• Is Part Of: International journal of biochemistry & cell biology. Volume 91:Part A(2017)
• Page Start: 45
• Page End: 52
• Publication Date: 2017-10
• Subjects: Baicalein -- Thioredoxin reductase -- Cancer stem cells -- ASK1 -- EL4; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2017.08.015
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Baicalein induces cell death in EL4 cells via inhibition of thioredoxin reductase. Highlights: Baicalein induced death in EL4 cells and modulated cellular redox. Baicalein suppressed thioredoxin reductase activity. Overexpression of thioredoxin abrogated antitumor effects of baicalein. CRISPR/Cas 9 based knock out of ASK1 abrogated antitumor effects of baicalein. Baicalein significantly reduced the tumor burden in lymphoma bearing mice. Abstract: We have earlier demonstrated the radioprotective potential of baicalein using murine splenic lymphocytes. Here, we have studied the effect of baicalein on murine T cell lymphoma EL4 cells and investigated the underlying mechanism of action. We observed that baicalein induced a dose dependent cell death in EL4 cells in vitro and significantly reduced the frequency of cancer stem cells. Previously, we have reported that murine and human T cell lymphoma cells have increased oxidative stress tolerance capacity due to active thioredoxin system. Hence, we monitored the effect of baicalein on thioredoxin system in EL4 cells. Docking studies revealed that baicalein could bind to the active site of thioredoxin reductase. Baicalein treatment led to significant reduction in the activity of thioredoxin reductase and nuclear levels of thioredoxin-1 thereby increasing ASK1 levels and caspase-3 activity. Interestingly, CRISPR-Cas9 based knock-out of ASK1 or over-expression of thioredoxin-1 abolished anti-tumor effects of baicalein in EL4 cells. Further, baicalein administration significantly reduced intra-peritoneal tumor burden of EL4 cells in C57BL/6 mice. Thus, our study describes anti-tumor effects of baicalein in EL4 cells via inhibition of thioredoxin system.