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Published:
Jul 9, 2021Keywords:
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Main Article Content
Cytotoxic activity of <i>lithospermum erythrorhizon</i> root extract against childhood acute leukemia cells via regulation of PI3K/AKT/mTOR pathway
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 (pAKT), total AKT (t-AKT), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (pmTOR) 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 dosedependently 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.
