title: β-2-himachalen-6-ol: A novel anticancer sesquiterpene unique to the Lebanese wild carrot.
abstract: Daucus carota ssp. carota, also known as wild carrot, is a commonly used herb in Lebanese folk medicine to treat several ailments including cancer. Previous studies in our laboratories showed that the Daucus carota oil extract (DCOE) and subsequent fractions exhibit antioxidant, anti-inflammatory and anti-cancer activities. In this study, we report the isolation and identification of the major compound responsible for the anti-cancer activity of DCOE along with the mechanism of action involved. GC-MS and NMR spectroscopy revealed the identity of the major compound as β-2-himachalen-6-ol, a novel sesquiterpene unique to the Lebanese wild carrot. β-2-Himachalen-6-ol demonstrated potent anti-cancer activity against B16F-10, Caco-2, MB-MDA-231, A549 and SF-268 cancer cells (IC50 13-4µg/ml; 58-18µM), with SF-268 cells being the most sensitive. The sesquiterpene was shown to induce cell death through apoptosis (flow cytometry), decrease 2D cell motility (wound healing assay) and 3D invasion, as well as increase cell adhesion in SF-268 cells. Additionally, β-2-himachalen-6-ol showed very low toxicity in mice with an LD50>6000mg/kg body weight. In conclusion, the present data demonstrate that β-2-himachalen-6-ol is a potential multi-mechanistic chemotherapeutic drug with high potency and safety.
authors.affiliation: Department of Natural Sciences, Lebanese American University, Byblos 1102 2801, Lebanon. Electronic address: robin.taleb@lau.edu.lb.
authors.forename: Robin I
authors.initials: RI
authors.lastname: Taleb
authors.affiliation: Department of Natural Sciences, Lebanese American University, Byblos 1102 2801, Lebanon.
authors.forename: Paul
authors.initials: P
authors.lastname: Najm
authors.affiliation: Department of Natural Sciences, Lebanese American University, Byblos 1102 2801, Lebanon.
authors.forename: Wassim
authors.initials: W
authors.lastname: Shebaby
authors.affiliation: Department of Natural Sciences, Lebanese American University, Byblos 1102 2801, Lebanon.
authors.forename: Joelle C
authors.initials: JC
authors.lastname: Boulos
authors.affiliation: Department of Natural Sciences, Lebanese American University, Byblos 1102 2801, Lebanon.
authors.forename: Sally
authors.initials: S
authors.lastname: Demirdjian
authors.affiliation: Department of Natural Sciences, Lebanese American University, Byblos 1102 2801, Lebanon.
authors.forename: Essa
authors.initials: E
authors.lastname: Hariri
authors.affiliation: Department of Natural Sciences, Lebanese American University, Byblos 1102 2801, Lebanon.
authors.forename: Mirvat
authors.initials: M
authors.lastname: El-Sibai
authors.affiliation: Department of Natural Sciences, Lebanese American University, Byblos 1102 2801, Lebanon.
authors.forename: Costantine
authors.initials: C
authors.lastname: Daher
authors.affiliation: School of Pharmacy, Lebanese American University, Byblos 1102 2801, Lebanon.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mroueh
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018552:Daucus carota / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012717:Sesquiterpenes; C000617228:beta-2-himachalen-6-ol; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 2-himachalen-6-ol (PubChem CID: 10537025); Cancer; Cell invasion; Cytotoxicity; Daucus carota; Wound healing; β-2-himachalen-6-ol; β-2-himachalen-6-ol (PubChem CID: n/a)