Chemopreventive and therapeutic effects of nimbolide in cancer: the underlying mechanisms.

Abstract

Cancer chemoprevention is a strategy taken to block, reverse or retard the multistep process of carcinogenesis, including the blockage of its vital morphogenetic milestones viz. normal-preneoplasia-neoplasia-metastasis. Naturally occurring phytochemicals are becoming increasingly popular over synthetic drugs for several reasons, including safety, efficacy and easy availability. Nimbolide, a triterpene derived from the leaves and flowers of neem, is widely used in traditional medical practices for treating various human ailments. The neem limonoid exhibits multiple pharmacological effects among which its anticancer activity is the most promising. The preclinical and mechanistic studies carried over the decades have shown that nimbolide inhibits tumorigenesis and metastasis without any toxicity and unwanted side effects. Nimbolide exhibits anticancer activity through selective modulation of multiple cell signaling pathways linked to inflammation, survival, growth, invasion, angiogenesis and metastasis. The present review highlights the current knowledge on molecular targets that contribute to the observed anticancer activity of nimbolide related to (i) inhibition of carcinogenic activation and induction of antioxidant and carcinogen detoxification enzymes, (ii) induction of growth arrest and apoptosis; and (iii) suppression of proinflammatory signaling pathways related to cancer progression.

• Authors: Lakshmi Narendra Bodduluru, Eshvendar Reddy Kasala, Nagaraju Thota, Chandana C Barua, Ramakrishna Sistla
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 28 Issue 5 Pg. 1026-35 (Aug 2014) ISSN: 1879-3177 [Electronic] England
• PMID: 24759803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Anticarcinogenic Agents
• Antineoplastic Agents
• Limonins
• nimbolide

Topics

• Animals
• Anticarcinogenic Agents (pharmacology, therapeutic use, toxicity)
• Antineoplastic Agents (pharmacology, therapeutic use, toxicity)
• Humans
• Limonins (pharmacology, therapeutic use, toxicity)
• Neoplasms (drug therapy, prevention & control)