Ferulenol, a Sesquiterpene Coumarin, Induce Apoptosis via Mitochondrial Dysregulation in Lung Cancer Induced by Benzo[a]pyrene: Involvement of Bcl2 Protein

• Published in: Anti-cancer agents in medicinal chemistry Vol. 17; no. 10; p. 1357
• Main Authors: Lariche, Nesrine, Lahouel, Mesbah, Benguedouar, Lamia, Zellagui, Ammar
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2017
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzo(a)pyrene; Cell Proliferation - drug effects; Cell Survival - drug effects; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - pharmacology; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Drug Screening Assays, Antitumor; Lung Neoplasms - chemically induced; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Mitochondria - drug effects; Mitochondria - metabolism; Molecular Structure; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Wistar; Structure-Activity Relationship; lung cancer; pro-oxidant; ferulenol; Benzo[a]pyrene; bcl2 protein; chemotherapeutic
• ISSN: 1875-5992
• DOI: 10.2174/1871520617666170213143444

Ferulenol, a sesquiterpene coumarin, was extracted from "Ferula vesceritensis" and possesses pro-oxidative and anticancer effects in different types of cancer. The objective of this study is to determine whether ferulenol has an anticancer effect by regulation the Bcl2 protein expression in lung cancer induced by benzo[a]pyrene in Wistar rats. Rats in group 1 have received, intraperitoneally, olive oil and considered as controls, animals of group 2 were treated with 100 mg/kg of benzo[a]pyrene intraperitoneally in order to induce lung cancer for 24 weeks, the 3rd groups of rats received the ferulenol 50 mg/kg intraperitoneally after 24 weeks of administration of benzo[a]pyrene and the last group, the rats were treated with ferulenol alone 50 mg/kg. Treatment with ferulenol significantly increased the rate of lipid peroxidation and decrease enzymatic (CAT and GST) and non-enzymatic (GSH) anti-oxidants in benzo[a]pyrene induced lung cancer. Anticancer efficacy of ferulenol was evaluated by down-regulation of Bcl2 protein and up-regulation of Bax protein, Therefore, ferulenol can alter the functionality of lung mitochondria by increasing the production of superoxide anion and mitochondrial swelling. Together, our results depict that ferulenol can be used as pro-oxidant and chemotherapeutic agent against lung cancer.