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Original Research Article | OPEN ACCESS

Cytotoxic activity of lithospermum erythrorhizon root extract against childhood acute leukemia cells via regulation of PI3K/AKT/mTOR pathway

Zhongxia Fu , Li Wang, Wei Zhang, Jingjing Wang, Shengdong Zhu, Wei Deng

Department of Pediatric Comprehensive Medicine, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou City, Gansu Province 730050, China;

For correspondence:-  Zhongxia Fu   Email: ZhongxiaFusdr@163.com   Tel:+869315188632

Accepted: 29 October 2019        Published: 30 November 2019

Citation: Fu Z, Wang L, Zhang W, Wang J, Zhu S, Deng W. Cytotoxic activity of lithospermum erythrorhizon root extract against childhood acute leukemia cells via regulation of PI3K/AKT/mTOR pathway. Trop J Pharm Res 2019; 18(11):2379-2394 doi: 10.4314/tjpr.v18i11.21

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the effect and mechanism of action of Lithospermum erythrorhizon root extract (LR) in childhood acute leukemia.
Methods: Human leukemic lymphoblast (CCRF-CEM cell line) cells were treated with LR (2, 4, and 8 mg/mL). Cell viability, cell apoptosis and cell cycle were measured using 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. The levels of cell-cycle-related proteins including cyclin D1, cyclin E1, cyclin-dependent kinase 2 (CDK2), CDK4 and CDK6, as well as cleaved caspase 3, cleaved caspase 9 and Bcl-2-associated x (Bax). Also determined were B-cell lymphoma-2 (Bcl-2), E-cadherin, N-cadherin, vimentin, zonula occludens 1 (ZO-1), matrix metalloproteinase-2 (MMP-2) and MMP-9. Cell migration and invasion were assessed using scratch and Transwell assays. Finally, phosphoinositide 3-kinase (PI3K), phosphorylated serine/threonine kinase (p-AKT), total AKT (t-AKT), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) were measured using western blotting.
Results: Lithospermum erythrorhizon root extract not only dose-dependently inhibited cell viability, induced G1 phase accumulation, and downregulated CDK2, CDK4, CDK6, cyclin D1, and cyclin E1, but also elevated apoptosis, cleaved caspase 3, cleaved caspase 9, and Bax and decreased Bcl-2 expression levels. In addition, Lithospermum erythrorhizon root extract suppressed migration and invasion of CCRF-CEM cells, downregulated N-cadherin, vimentin, MMP-2, and MMP-9, and upregulated E-cadherin and ZO-1. Moreover, Lithospermum erythrorhizon root extracts dose-dependently inhibited PI3K, p-AKT (ser473)/t-AKT, p-mTOR (ser2448)/mTOR, and p-mTOR (ser2481)/mTOR.
Conclusion: The findings provide a potential therapeutic approach to the treatment of childhood acute leukemia.

Keywords: Childhood acute leukemia, PI3K/AKT/mTOR pathway Lithospermum erythrorhizon root extracts

Impact Factor
Thompson Reuters (ISI): 0.523 (2021)
H-5 index (Google Scholar): 39 (2021)

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