title: B-9-3, a novel β-carboline derivative exhibits anti-cancer activity via induction of apoptosis and inhibition of cell migration in vitro.
abstract: Peganum harmala L is an important medicinal plant that has been used from ancient time due to its alkaloids rich of ß-carbolines. Harmane is a naturally occurring ß-carboline extracted from Peganum harmala L, that exhibits a wide range of biological, psychopharmacological, and toxicological actions. The synthesis of novel derivatives with high anti-cancer activity and less side effects is necessary. In the present study, B-9-3-a semi-synthetic compound that is formed of two harmane molecules bound by a butyl group-showed a strong anti-cancer activity against a human lung cancer cell line, a human breast cancer cell line, and a human colorectal carcinoma cell line. B-9-3 anti-proliferative effect followed a similar pattern in the three cell lines. This pattern includes a dose-dependent induction of apoptosis, or necroptosis as confirmed by Hoechst staining, flow cytometry and western blot analyses, and the inhibition of cancer cells migration that was shown to be dependent on the drug׳s concentration as well. Moreover, B-9-3 inhibited tube formation in human umbilical vascular endothelial cell line (HUVEC), which indicates an anti-angiogenesis activity in vitro. In summary, B-9-3, a semi-synthetic derivative of ß-carboline, has an anti-proliferative effect against tumor cells via induction of apoptosis and inhibition of cell migration.
authors.affiliation: New Drug Screening Center, China Pharmaceutical University, 24 Tongjia Road, Nanjing 210009, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China.
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Daoud
authors.affiliation: New Drug Screening Center, China Pharmaceutical University, 24 Tongjia Road, Nanjing 210009, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.affiliation: New Drug Screening Center, China Pharmaceutical University, 24 Tongjia Road, Nanjing 210009, PR China.
authors.forename: Feiyang
authors.initials: F
authors.lastname: Xiao
authors.affiliation: New Drug Screening Center, China Pharmaceutical University, 24 Tongjia Road, Nanjing 210009, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, China. Electronic address: shangjing21cn@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D032443:Peganum
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002243:Carbolines
keywords: Anti-tumor; Harmane; Necro-apoptosis; Peganum harmala L