Oncotarget

Reviews:

Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development

Lingzhi Wang, Do Dang Khoa Phan, Jingwen Zhang, Pei-Shi Ong, Win Lwin Thuya, Ross Soo, Andrea Li-Ann Wong, Wei Peng Yong, Soo Chin Lee, Paul Chi-Lui Ho, Gautam Sethi _ and Boon Cher Goh

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Oncotarget. 2016; 7:44790-44802. https://doi.org/10.18632/oncotarget.8316

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Abstract

Lingzhi Wang1,2, Do Dang Khoa Phan1,3, Jingwen Zhang2, Pei-Shi Ong3, Win Lwin Thuya1,3, Ross Soo1,4, Andrea Li-Ann Wong1,4, Wei Peng Yong1,4, Soo Chin Lee1,4, Paul Chi-Lui Ho3, Gautam Sethi2 and Boon Cher Goh1,2,4

1 Cancer Science Institute of Singapore, National University of Singapore, Singapore

2 Department of Pharmacology, National University Health System, Singapore

3 Department of Pharmacy, National University of Singapore, Singapore

4 Department of Haematology-Oncology, National University Health System, Singapore

Correspondence to:

Boon Cher Goh , email:

Gautam Sethi , email:

Keywords: nimbolide, anticancer property, pharmacodynamics, pharmacokinetics, toxicology

Received: January 10, 2016 Accepted: March 07, 2016 Published: March 24, 2016

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.


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