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Azadirachta indica (Neem) and Neem Limonoids as Anticancer Agents: Molecular Mechanisms and Targets

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Perspectives in Cancer Prevention-Translational Cancer Research

Abstract

Neem (Azadirachta indica A. Juss), one of the most versatile medicinal plants that grows ubiquitously in India has attained worldwide prominence owing to its wide range of medicinal properties. The bioactivity of neem has been attributed to its rich content of complex limonoids. Neem extracts and limonoids have been documented to exert antiproliferative effects both in vitro and in vivo. Accumulating evidence indicates that the anticancer effects of neem extracts and neem limonoids are mediated by preventing carcinogen activation; enhancing host antioxidant and detoxification systems; inhibiting cell proliferation, inflammation, invasion and angiogenesis; inducing apoptosis; modulating oncogenic transcription factors and signalling kinases; and influencing the epigenome. Neem and its constituent limonoids that target multiple signalling pathways aberrant in cancer are promising candidates for anticancer drug development.

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Abbreviations

Apaf-1:

Apoptosis associated factor-1

Bcl-2:

B-cell lymphoma-2

B(a)P:

Benzo(a)pyrene

CDK:

Cyclin-dependent kinases

DR:

Death receptor

Dvl:

Dishevelled

DMBA:

7,12-dimethylbenz(a)anthracene

ECM:

Extracellular matrix

ERK:

Extracellular signal-regulatedkinase

GSK-3β:

Glycogen synthase kinase 3 beta

HDAC:

Histone deacetylase

HIF-1α:

Hypoxia-inducible factor 1α

IAPs:

Inhibitors of apoptosis proteins

IκB-α:

Inhibitor of kappa B alpha

IKK:

IκB kinase

IL:

Interleukin

JNK:

c-Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloproteinases

MTMP:

Mitochondrial permeability transition pore

NF-κB:

Nuclear factor kappa B

NLGP:

Neem leaf glycoproteins

PCNA:

Proliferating cell nuclear antigen

PARP:

Poly(ADP-ribose) polymerase

PI3K:

Phosphoinositide 3-kinase

RECK:

Reversion-inducing cysteine-rich protein with Kazal motifs

ROS:

Reactive oxygen species

Smac/Diablo:

Second mitochondria derived activator of caspases/direct IAP binding protein with low pI

TIMP-2:

Tissue inhibitor of matrix metalloproteinases-2

TNF:

Tumour necrosis factor

TRAIL:

TNF-related apoptosis-inducing ligand

Ub:

Ubiquitin ligase

VEGF:

Vascular endothelial growth factor

XME:

Xenobiotic metabolizing enzyme

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Acknowledgements

The authors gratefully acknowledge financial support from the Department of Science and Technology, Government of India, New Delhi, India.

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  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India

    Siddavaram Nagini & Ramamurthi Vidya Priyadarsini

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  1. Siddavaram Nagini
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  2. Ramamurthi Vidya Priyadarsini
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Correspondence to Siddavaram Nagini .

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  1. Computational Biology & Bioinformatics, University of Kerala, Kariavattom, Trivandrum, Kerala, India

    Perumana R. Sudhakaran

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Nagini, S., Priyadarsini, R.V. (2014). Azadirachta indica (Neem) and Neem Limonoids as Anticancer Agents: Molecular Mechanisms and Targets. In: R. Sudhakaran, P. (eds) Perspectives in Cancer Prevention-Translational Cancer Research. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1533-2_4

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