Chemopreventive and therapeutic effects of nimbolide in cancer: the underlying mechanisms.
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.
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India. Electronic address: laxmi.naren21@gmail.com.
Lakshmi Narendra
LN
Bodduluru
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India. Electronic address: ishreddy4@gmail.com.
Eshvendar Reddy
ER
Kasala
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India. Electronic address: thotanagaraj12@gmail.com.
Nagaraju
N
Thota
Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati 781032, Assam, India. Electronic address: chanacin@gmail.com.
Chandana C
CC
Barua
Medicinal Chemistry & Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500007, Andhra Pradesh, India. Electronic address: sistla@iict.res.in.
Ramakrishna
R
Sistla
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D036701:Limonins / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D036701:Limonins; C042198:nimbolide
Apoptosis; Cancer; Chemoprevention; NF-κB; Nimbolide