Anticancer activity of limonene: A systematic review of target signaling pathways

Limonene (LIM) is a monoterpene, which is abundant in essential oils of Citrus fruits peels (Rutaceae). More recently, LIM, as a potential natural anticancer compound, has attracted major attention and exerted a chemopreventive activity, stimulating the detoxification of carcinogenic compounds and l...

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Bibliographic Details
Published in:Phytotherapy research 2021-09, Vol.35 (9), p.4957-4970
Main Authors: Araújo‐Filho, Heitor Gomes de, Santos, Jucilene F., Carvalho, Mikaella T. B., Picot, Laurent, Fruitier‐Arnaudin, Ingrid, Groult, Hugo, Quintans‐Júnior, Lucindo J., Quintans, Jullyana S.S.
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Angiogenesis
Anticancer properties
Antitumor activity
Apoptosis
Biochemistry
Biochemistry, Molecular Biology
Cancer
Carcinogens
Caspase
chemopreventive activity
Chemoresistance
Citrus fruits
Cytochrome
Cytochrome c
Cytochromes
Detoxification
Essential oils
Insulin-like growth factor II receptors
Life Sciences
Limonene
molecular mechanisms
monoterpene
natural product
Raf protein
Signal transduction
Signaling
Toxicity
Tumors
Vascular endothelial growth factor
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Summary:Limonene (LIM) is a monoterpene, which is abundant in essential oils of Citrus fruits peels (Rutaceae). More recently, LIM, as a potential natural anticancer compound, has attracted major attention and exerted a chemopreventive activity, stimulating the detoxification of carcinogenic compounds and limiting tumor growth and angiogenesis in various cancer models. Twenty‐six (26) articles were selected based on previously established criteria. Anticancer activity of LIM was related to the inhibition of tumor initiation, growth, and angiogenesis and the induction of cancer cells apoptosis. LIM was able to increase Bax expression, release cytochrome c, and activate the caspase pathway. In addition, LIM increased the expression of p53 and decreased the activity of Ras/Raf/MEK/ERK and PI3K/Akt pathways. LIM also decreased the expression of VEGF and increased the activities of the Man‐6‐P / IGF2R and TGF‐βIIR receptors. These results highlight LIM as an abundant natural molecule with low toxicity and pleiotropic pharmacological activity in cancer cells, targeting various cell‐signaling pathways critically involved in the initiation, growth, and chemoresistance of cancer cells.
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.7125