Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.8316
Title: Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development
Authors: Wang, L 
Khoa Phan, D.D
Zhang, J
Ong, P.-S 
Thuya, W.L 
Soo, R.A 
Wong, A.L.-A 
Yong, W.P 
Lee, S.C 
Ho, P.C.-L 
Sethi, G 
Goh, B.C 
Keywords: nimbolide
resveratrol
romidepsin
limonoid
nimbolide
plant extract
acute toxicity
angiogenesis
antineoplastic activity
antioxidant activity
apoptosis
blood brain barrier
cell cycle G0 phase
cell migration
chemoprophylaxis
cytotoxicity
drug absorption
drug accumulation
drug bioavailability
drug blood level
drug determination
drug efficacy
drug elimination
drug half life
drug isolation
drug metabolism
drug potency
drug potentiation
drug safety
drug structure
flow cytometry
G1 phase cell cycle checkpoint
high performance liquid chromatography
human
IC50
in vitro study
in vivo study
LD50
nonhuman
phase 1 clinical trial (topic)
phase 2 clinical trial (topic)
Review
animal
Azadirachta indica
cell proliferation
chemistry
drug effects
neoplasm
neovascularization (pathology)
phytotherapy
procedures
vascularization
Animals
Apoptosis
Azadirachta
Cell Proliferation
Humans
Limonins
Neoplasms
Neovascularization, Pathologic
Phytotherapy
Plant Extracts
Issue Date: 2016
Citation: Wang, L, Khoa Phan, D.D, Zhang, J, Ong, P.-S, Thuya, W.L, Soo, R.A, Wong, A.L.-A, Yong, W.P, Lee, S.C, Ho, P.C.-L, Sethi, G, Goh, B.C (2016). Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development. Oncotarget 7 (28) : 44790-44802. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.8316
Abstract: Nimbolide is one of the main components in the leaf extract of Azadirachta indica (A. indica). Accumulating evidence from various in vitro and in vivo studies indicates that nimbolide possesses potent anticancer activity against several types of cancer and also shows potential chemopreventive activity in animal models. The main mechanisms of action of nimbolide include anti-proliferation, induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of carcinogen-metabolizing enzymes. Although multiple pharmacodynamic (PD) studies have been carried out, nimbolide is still at the infant stage in the drug development pipeline due to the lack of systematic pharmacokinetic (PK) studies and long-term toxicological studies. Preclinical PK and toxicological studies are vital in determining the dosage range to support the safety of nimbolide for first-in-human clinical trials. In this review, we will provide a comprehensive summary for the current status of nimbolide as an anticancer and chemopreventive lead compound, and highlight the importance of systematic preclinical PK and toxicological studies in accelerating the process of application of nimbolide as a therapeutic agent against various malignancies.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/174111
ISSN: 19492553
DOI: 10.18632/oncotarget.8316
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