The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis.
The neem tree has attracted considerable research attention as a rich source of limonoids that have potent antioxidant and anti-cancer properties. The present study was designed to evaluate the chemopreventive potential of the neem limonoids azadirachtin and nimbolide based on in vitro antioxidant assays and in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Both azadirachtin and nimbolide exhibited concentration-dependent anti-radical scavenging activity and reductive potential in the order: nimbolide > azadirachtin > ascorbate. Administration of both azadirachtin and nimbolide inhibited the development of DMBA-induced HBP carcinomas by influencing multiple mechanisms including prevention of procarcinogen activation and oxidative DNA damage, upregulation of antioxidant and carcinogen detoxification enzymes and inhibition of tumour invasion and angiogenesis. On a comparative basis, nimbolide was found to be a more potent antioxidant and chemopreventive agent and offers promise as a candidate agent in multitargeted prevention and treatment of cancer.
Priyadarsini
Ramamurthi Vidya
RV
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
Manikandan
Palrasu
P
Kumar
Gurram Harish
GH
Nagini
Siddavaram
S
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001483:Base Sequence; D002610:Cheek; D006224:Cricetinae; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D036701:Limonins / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D015262:Xenobiotics / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D017931:DNA Primers; D004798:Enzymes; D016166:Free Radical Scavengers; D036701:Limonins; D015262:Xenobiotics; C042198:nimbolide; D015127:9,10-Dimethyl-1,2-benzanthracene; C010329:azadirachtin