Oxidative stress mediated cytotoxicity in leukemia cells induced by active phyto-constituents isolated from traditional herbal drugs of West Bengal
Autor: | Santanu Kar Mahapatra, Vellingiri Vadivel, Monaj Kumar Sarkar |
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Rok vydání: | 2020 |
Předmět: |
Cell Survival
Phytochemicals Vitexin India HL-60 Cells Flacourtia Pharmacology Jurkat cells Lipid peroxidation Jurkat Cells 03 medical and health sciences chemistry.chemical_compound Prosopis 0302 clinical medicine hemic and lymphatic diseases Cineraria Drug Discovery medicine Humans 030304 developmental biology 0303 health sciences Leukemia biology Plant Extracts Myeloid leukemia medicine.disease biology.organism_classification Antineoplastic Agents Phytogenic Plant Leaves Oxidative Stress chemistry Flacourtia indica 030220 oncology & carcinogenesis Plant Bark Madhuca Medicine Traditional K562 Cells Reactive Oxygen Species Myricitrin |
Zdroj: | Journal of Ethnopharmacology. 251:112527 |
ISSN: | 0378-8741 |
DOI: | 10.1016/j.jep.2019.112527 |
Popis: | Ethnopharmacological relevance In search of safe and effective therapeutic agents as alternative to synthetic chemotherapeutics for the treatment of leukemia, the herbal drugs (Leaf of Madhuca longifolia, leaf of Prosopis cineraria and bark of Flacourtia indica) with long traditional use in West Bengal have received our attention. Aim of the study Present work was conducted to isolate and identify the active compounds of the selected herbal drugs using bio-assay guided fractionation and also to investigate their anticancer mechanism in leukemia cell lines. Materials and methods Bio-assay guided fractionation was used for the isolation of active constituents such as myricitrin, vitexin and vanillin from the aqueous extracts of M. longifolia, P. cineraria and F. indica, respectively using liquid partitioning and column chromatography and the compounds were characterized by HPLC, MS and NMR. Dose and time-dependent cytotoxicity of isolated compounds were studied against leukemia cells and their anticancer mechanism such as cell wall damage, nuclear damage, ROS and NO generation, SOD level, LDH release and lipid peroxidation were investigated. Results Aqueous extract of M. longifolia, P. cineraria and F. indica exhibited maximum anti-proliferative activity against HL-60 (Acute myeloid leukemia, AML, 72.06%), K-562 (Chronic myeloid leukemia, CML, 42.14%) and Jurkat (Acute lymphoblastic leukemia, ALL, 51.71%) cells. Myricitrin, vitexin and vanillin exhibited dose-dependent (IC-50 values 164.4, 147 & 29.22 μg/ml) and time-dependent activity with maximum cytotoxicity at 48 h. All these three compounds caused apoptosis in leukemia cells by inducing free radicals such as ROS (1.33–2.65 Arbitrary units) and NO (11.17–18.53 μM), cell membrane damage and nuclear condensation which were evidenced by increased release of LDH (1326–1439 U/L), improved lipid peroxidation (10.19–14.41 nM/mg protein) and reduced SOD level (6.2–9.21 U/mg protein) in leukemia cells. Conclusions Based on anti-proliferative activity, the isolated phyto-compounds myrcitrin, vitexin and vanillin from M. longifolia, P. cineraria and F. indica could be developed as natural drugs for treating AML, CML and ALL leukemia types, respectively. |
Databáze: | OpenAIRE |
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