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Journal of Cancer Prevention

Original Article

J Cancer Prev 2019; 24(1): 11-19

Published online March 30, 2019

https://doi.org/10.15430/JCP.2019.24.1.11

© Korean Society of Cancer Prevention

Induction of Apoptosis Scutellaria baicalensis Georgi Root Extract by Inactivation of the Phosphatidyl Inositol 3-kinase/Akt Signaling Pathway in Human Leukemia U937 Cells

Eun Ok Choi1,2, Hye-Jin Hwang2,3, Yung Hyun Choi1,2

1Department of Biochemistry, Dong-Eui University College of Korean Medicine, 2Anti-Aging Research Center, Dong-Eui University, 3Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dong-Eui University, Busan, Korea

Correspondence to :
Yung Hyun Choi
E-mail: choiyh@deu.ac.kr, ORCID: Yung Hyun Choi, https://orcid.org/0000-0002-1454-3124

Received: February 26, 2019; Revised: March 18, 2019; Accepted: March 18, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The roots of Scutellaria baicalensis Georgi (Labiatae) have been widely used in traditional medicine for treatment of various diseases. In this study, we investigated the effects of ethanol extracts of S. baicalensis roots (EESB) on the growth ofn human leukemia U937 cells.

Methods

The effect of EESB on cell viability was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apoptosis was determined using 4,6-diamidino-2-phenyllindile staining and flow cytometry. The effects of EESB on the expression of regulatory proteins of apoptosis and phosphatidyl inositol 3-kinase (PI3K)/Akt signaling were determined by Western blotting. Caspase activity and mitochondrial membrane potential (MMP) were measured using flow cytometric analysis.

Results

EESB significantly inhibited the growth of U937 cells and induced apoptosis, which was associated with down-regulation of anti-apoptotic Bcl-2, up-regulation of pro-apoptotic Bax, the loss of MMP and activation of caspase-9 and -3. We also found that EESB enhanced the expression of death receptors (DRs) and their associated ligands and induced the activation of caspase-8 and truncation of Bid. In addition, EESB suppressed PI3K/Akt signaling and EESB-induced apoptosis and growth inhibition were further increased by inhibition of PI3K activity.

Conclusions

Our results indicated that the pro-apoptotic effect of EESB was mediated through the activation of DR-mediated intrinsic and mitochondria-mediated extrinsic apoptosis pathways and inhibition of the PI3K/Akt signaling in U937 cells.

Keywords: Scutellaria baicalensis, U937 cells, Apoptosis, Caspase, PI3K/Akt

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