Myristicin from nutmeg induces apoptosis via the mitochondrial pathway and down regulates genes of the DNA damage response pathways in human leukaemia K562 cells

C Martins, Carolina Doran, Inês C Silva, Cláudia Miranda, José Rueff, AS Rodrigues

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13 Citations (Scopus)

Abstract

Myristicin, an allylbenzene, is a major active component of various spices, such as nutmeg and cinnamon, plants from the Umbelliferae family or in some essential oils, such as oils of clove or marjoram. Human exposure to myristicin is low but widespread due to consumption of these spices and essential oils, added to food (e.g. cola drinks) or in traditional medicine. Occasionally high dose exposure occurs, leading to various clinical symptoms, however the molecular mechanisms underlying them are unknown. Our previous studies revealed that myristicin is not genotoxic and yet presented apoptotic activity. Therefore, in this work we assessed the apoptotic mechanisms induced by myristicin in human leukaemia cells. In order to gain further insight on the potential of myristicin to modulate gene expression we also analysed alterations in expression of 84 genes associated with the DNA damage response pathway. The results obtained show that myristicin can induce apoptosis as characterised by alterations in the mitochondrial membrane potential, cytochrome c release, caspase-3 activation, PARP-cleavage and DNA fragmentation. The gene expression profile revealed an overall down regulation of DNA damage response genes after exposure to myristicin, with significant under-expression of genes associated with nucleotide excision repair (ERCC1), double strand break repair (RAD50, RAD51) and DNA damage signalling (ATM) and stress response (GADD45A, GADD45G). On the whole, we demonstrate that myristicin can alter mitochondrial membrane function, induce apoptosis and modulate gene expression in human leukaemia K562 cells. This study provides further detail on the molecular mechanisms underlying the biological activity of myristicin. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalChemico-Biological Interactions
Volume218
Issue numberNA
DOIs
Publication statusPublished - 2014

Fingerprint

Myristica fragrans
K562 Cells
DNA Damage
Leukemia
Down-Regulation
Genes
Apoptosis
DNA
Gene expression
Gene Expression
Spices
Volatile Oils
Repair
Clove Oil
Apiaceae
Cinnamomum zeylanicum
Origanum
Membranes
myristicin
Mitochondrial Membrane Potential

Keywords

  • Myristicin
  • Leukaemia
  • Apoptosis
  • Mitochondria
  • Gene expression

Cite this

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title = "Myristicin from nutmeg induces apoptosis via the mitochondrial pathway and down regulates genes of the DNA damage response pathways in human leukaemia K562 cells",
abstract = "Myristicin, an allylbenzene, is a major active component of various spices, such as nutmeg and cinnamon, plants from the Umbelliferae family or in some essential oils, such as oils of clove or marjoram. Human exposure to myristicin is low but widespread due to consumption of these spices and essential oils, added to food (e.g. cola drinks) or in traditional medicine. Occasionally high dose exposure occurs, leading to various clinical symptoms, however the molecular mechanisms underlying them are unknown. Our previous studies revealed that myristicin is not genotoxic and yet presented apoptotic activity. Therefore, in this work we assessed the apoptotic mechanisms induced by myristicin in human leukaemia cells. In order to gain further insight on the potential of myristicin to modulate gene expression we also analysed alterations in expression of 84 genes associated with the DNA damage response pathway. The results obtained show that myristicin can induce apoptosis as characterised by alterations in the mitochondrial membrane potential, cytochrome c release, caspase-3 activation, PARP-cleavage and DNA fragmentation. The gene expression profile revealed an overall down regulation of DNA damage response genes after exposure to myristicin, with significant under-expression of genes associated with nucleotide excision repair (ERCC1), double strand break repair (RAD50, RAD51) and DNA damage signalling (ATM) and stress response (GADD45A, GADD45G). On the whole, we demonstrate that myristicin can alter mitochondrial membrane function, induce apoptosis and modulate gene expression in human leukaemia K562 cells. This study provides further detail on the molecular mechanisms underlying the biological activity of myristicin. (C) 2014 Elsevier Ireland Ltd. All rights reserved.",
keywords = "POST-LABELING ANALYSIS, ADDUCTS, Gene expression, Apoptosis, NATURALLY-OCCURRING ALKENYLBENZENES, CANCER CHEMOPREVENTION, Mitochondria, Myristicin, ESSENTIAL OILS, BETA-ASARONE, DIETARY PHYTOCHEMICALS, SAFROLE, Leukaemia, ESTRAGOLE, PREVENTION, Myristicin, Leukaemia, Apoptosis, Mitochondria, Gene expression",
author = "C Martins and Carolina Doran and Silva, {In{\^e}s C} and Cl{\'a}udia Miranda and Jos{\'e} Rueff and AS Rodrigues",
year = "2014",
doi = "10.1016/j.cbi.2014.04.014",
language = "English",
volume = "218",
pages = "1--9",
journal = "Chemico-Biological Interactions",
issn = "0009-2797",
publisher = "Elsevier Science B.V., Amsterdam.",
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TY - JOUR

T1 - Myristicin from nutmeg induces apoptosis via the mitochondrial pathway and down regulates genes of the DNA damage response pathways in human leukaemia K562 cells

AU - Martins, C

AU - Doran, Carolina

AU - Silva, Inês C

AU - Miranda, Cláudia

AU - Rueff, José

AU - Rodrigues, AS

PY - 2014

Y1 - 2014

N2 - Myristicin, an allylbenzene, is a major active component of various spices, such as nutmeg and cinnamon, plants from the Umbelliferae family or in some essential oils, such as oils of clove or marjoram. Human exposure to myristicin is low but widespread due to consumption of these spices and essential oils, added to food (e.g. cola drinks) or in traditional medicine. Occasionally high dose exposure occurs, leading to various clinical symptoms, however the molecular mechanisms underlying them are unknown. Our previous studies revealed that myristicin is not genotoxic and yet presented apoptotic activity. Therefore, in this work we assessed the apoptotic mechanisms induced by myristicin in human leukaemia cells. In order to gain further insight on the potential of myristicin to modulate gene expression we also analysed alterations in expression of 84 genes associated with the DNA damage response pathway. The results obtained show that myristicin can induce apoptosis as characterised by alterations in the mitochondrial membrane potential, cytochrome c release, caspase-3 activation, PARP-cleavage and DNA fragmentation. The gene expression profile revealed an overall down regulation of DNA damage response genes after exposure to myristicin, with significant under-expression of genes associated with nucleotide excision repair (ERCC1), double strand break repair (RAD50, RAD51) and DNA damage signalling (ATM) and stress response (GADD45A, GADD45G). On the whole, we demonstrate that myristicin can alter mitochondrial membrane function, induce apoptosis and modulate gene expression in human leukaemia K562 cells. This study provides further detail on the molecular mechanisms underlying the biological activity of myristicin. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

AB - Myristicin, an allylbenzene, is a major active component of various spices, such as nutmeg and cinnamon, plants from the Umbelliferae family or in some essential oils, such as oils of clove or marjoram. Human exposure to myristicin is low but widespread due to consumption of these spices and essential oils, added to food (e.g. cola drinks) or in traditional medicine. Occasionally high dose exposure occurs, leading to various clinical symptoms, however the molecular mechanisms underlying them are unknown. Our previous studies revealed that myristicin is not genotoxic and yet presented apoptotic activity. Therefore, in this work we assessed the apoptotic mechanisms induced by myristicin in human leukaemia cells. In order to gain further insight on the potential of myristicin to modulate gene expression we also analysed alterations in expression of 84 genes associated with the DNA damage response pathway. The results obtained show that myristicin can induce apoptosis as characterised by alterations in the mitochondrial membrane potential, cytochrome c release, caspase-3 activation, PARP-cleavage and DNA fragmentation. The gene expression profile revealed an overall down regulation of DNA damage response genes after exposure to myristicin, with significant under-expression of genes associated with nucleotide excision repair (ERCC1), double strand break repair (RAD50, RAD51) and DNA damage signalling (ATM) and stress response (GADD45A, GADD45G). On the whole, we demonstrate that myristicin can alter mitochondrial membrane function, induce apoptosis and modulate gene expression in human leukaemia K562 cells. This study provides further detail on the molecular mechanisms underlying the biological activity of myristicin. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

KW - POST-LABELING ANALYSIS

KW - ADDUCTS

KW - Gene expression

KW - Apoptosis

KW - NATURALLY-OCCURRING ALKENYLBENZENES

KW - CANCER CHEMOPREVENTION

KW - Mitochondria

KW - Myristicin

KW - ESSENTIAL OILS

KW - BETA-ASARONE

KW - DIETARY PHYTOCHEMICALS

KW - SAFROLE

KW - Leukaemia

KW - ESTRAGOLE

KW - PREVENTION

KW - Myristicin

KW - Leukaemia

KW - Apoptosis

KW - Mitochondria

KW - Gene expression

U2 - 10.1016/j.cbi.2014.04.014

DO - 10.1016/j.cbi.2014.04.014

M3 - Article

VL - 218

SP - 1

EP - 9

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

SN - 0009-2797

IS - NA

ER -