Abstract
ABSTACT Artemisia nilagirica (Clarke) is a widely used medicinal herb in Indian traditional system of medicine. Therefore, the present study was designed to evaluate the effects of A. nilagirica extracts/fractions on inhibition of proliferation and apoptosis in a human monocytic leukemia (THP-1) cell line. The crude extracts (A. nilagirica ethyl acetate extract [ANE] and A. nilagirica methanolic extract [ANA]) showed cytotoxic activity toward THP-1 cells with the IC50 values of 38.21 ± 7.37 and 132.41 ± 7.19 µg/ml, respectively. However, the cytotoxic activity of active fractions (ANE-B and ANM-9) obtained after column chromatography was found to be much more pronounced than their parent extracts. The IC50 values of ANE-B and ANM-9 were found to be 27.04 ± 2.54 µg/ml and 12.70 ± 4.79 µg/ml, respectively, suggesting greater susceptibility of the malignant cells. Cell cycle analysis and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) assay revealed that inhibition of cell growth by A. nilagirica fractions on THP-1 cells was mediated by apoptosis. Active fractions of A. nilagirica increased the expression levels of caspase-3, -7, and poly-ADP-ribose polymerase (PARP), a critical member of the apoptotic pathway. These results suggested that active fractions of A. nilagirica may play a promising role in growth suppression by inducing apoptosis in human monocytic leukemic cells via mitochondria-dependent and death receptor-dependent apoptotic pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anticarcinogenic Agents / adverse effects
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Anticarcinogenic Agents / chemistry
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Anticarcinogenic Agents / isolation & purification*
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Anticarcinogenic Agents / pharmacology
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Antineoplastic Agents, Phytogenic / adverse effects
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / isolation & purification*
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Antineoplastic Agents, Phytogenic / pharmacology
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Apoptosis / drug effects*
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Artemisia / chemistry*
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Biological Assay
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Caspase 3 / chemistry
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Caspase 7 / chemistry
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Caspase 7 / genetics
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Caspase 7 / metabolism
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Cell Proliferation / drug effects
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Cells, Cultured
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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India
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Inhibitory Concentration 50
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Leukemia, Monocytic, Acute / drug therapy*
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Leukemia, Monocytic, Acute / metabolism
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Leukemia, Monocytic, Acute / pathology
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / drug effects*
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Mice, Inbred BALB C
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Neoplasm Proteins / agonists
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Plant Extracts / adverse effects
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Plant Extracts / chemistry
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology
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Poly(ADP-ribose) Polymerases / chemistry
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Poly(ADP-ribose) Polymerases / genetics
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Poly(ADP-ribose) Polymerases / metabolism
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THP-1 Cells
Substances
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Anticarcinogenic Agents
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Antineoplastic Agents, Phytogenic
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Neoplasm Proteins
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Plant Extracts
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Poly(ADP-ribose) Polymerases
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Caspase 3
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Caspase 7