Total coumarins of Hedyotis diffusa induces apoptosis of myelodysplastic syndrome SKM-1 cells by activation of caspases and inhibition of PI3K/Akt pathway proteins.

6533b85cfe1ef96bd12bcb5d

RESEARCH PRODUCT

Total coumarins of Hedyotis diffusa induces apoptosis of myelodysplastic syndrome SKM-1 cells by activation of caspases and inhibition of PI3K/Akt pathway proteins.

Bo Wang Baodong Ye Shengyun Lin Letian Shan Wenbin Qian Jing Li Thomas Efferth Jianping Jiang

subject

0301 basic medicine Apoptosis Pharmacology Cell Line Hedyotis diffusa 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Western blot Coumarins Drug Discovery medicine Hedyotis Humans MTT assay PI3K/AKT/mTOR pathway Caspase Cells Cultured Cell Proliferation Pharmacology Hedyotis medicine.diagnostic_test biology business.industry Akt/PKB signaling pathway Mesenchymal Stem Cells biology.organism_classification 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Caspases Myelodysplastic Syndromes Immunology biology.protein business Proto-Oncogene Proteins c-akt

description

Abstract Ethnopharmacological relevance Hedyotis diffusa is an ethno-medicine used for anti-cancer treatment in the clinic of traditional Chinese medicine (TCM). The total coumarins of Hedyotis diffusa (TCHD) was a selected extract with observed antiproliferative activity, which has not been tested in treatment of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Aim of the study This study aimed to evaluate the apoptosis-inducing effect of TCHD on human MDS cell line (SKM-1) and explore its action mechanism in association with caspase family and PI3K/Akt signaling pathway. Materials and methods The chemical constituents and total coumarins content of TCHD were determined by High Performance Liquid Chromatography-tandem mass spectrometry (HPLC-MS/MS) and UV–vis spectrophotometry, respectively. MTT assay, Hoechst 33258 staining, and Annexin V-FITC/PI double labeling were applied to evaluate TCHD's efficacy on SKM-1 cells. Western blot analysis was also used to clarify the action mechanism of TCHD on protein expression level. Results Two compounds, p-coumaric acid and E-6-O-p-coumaroyl scandoside methyl ester, were identified in TCHD, and its total coumarins content reached 87.4%. By MTT assay, apoptosis-inducing effect of TCHD on SKM-1 cells was found in a dose-dependent manner after 24–48 h treatment, with IC50 values of 104.48 μg/ml and 100.66 μg/ml, respectively. Morphological and flow cytometry observation also confirmed such effect of TCHD. Western blot analysis clarified its action mechanism associating with the activation of caspases and inhibition of PI3K/Akt pathway proteins. Conclusions This is the first report regarding the apoptosis-inducing efficacy and mechanism of TCHD on SKM-1 cells, providing a promising candidate of TCM for MDS and AML therapy with fewer side effects.

year	journal	country	edition	language
2016-01-17	Journal of ethnopharmacology

10.1016/j.jep.2016.12.012 https://pubmed.ncbi.nlm.nih.gov/27988397