title: Antiproliferative activity of violaxanthin isolated from bioguided fractionation of Dunaliella tertiolecta extracts.
abstract: Dunaliella tertiolecta (DT) was chemically investigated to isolate molecules inhibiting cancer cell proliferation and inducing apoptosis in vitro. The potency to inhibit cell growth was used for the bio-guided fractionation and isolation of active compounds using chromatographic techniques. The DT dichloromethane extract exhibited a strong anti-proliferative activity on MCF-7 and LNCaP cells, and was further fractionated and sub-fractionated by RP-HPLC. High resolution mass spectrometry and spectrophotometric analysis unequivocally identified violaxanthin as the most antiproliferative molecule present in DT DCM extract. Violaxanthin purified from DT induced MCF-7 dose-dependent growth inhibition in continuous and discontinuous treatments, at concentrations as low as 0.1 μg·mL⁻¹ (0.17 μM). Phosphatidylserine exposure, typical of early apoptosis, was observed after 48 h treatment at 8 μg·mL⁻¹ (13.3 μM) but no DNA fragmentation, characteristic of late apoptosis steps, could be detected even after 72 h treatment at 40 μg·mL⁻¹ (66.7 μM). Taken together, our results demonstrate the strong antiproliferative activity of violaxanthin on one human mammary cancer cell line, and suggest that studying the pharmacology of violaxanthin and pharmacomodulated derivatives on cancer cells may allow potent antiproliferative drugs to be obtained.
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Pasquet
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Morisset
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Said
authors.initials: S
authors.lastname: Ihammouine
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Chepied
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Aumailley
authors.affiliation: IFREMER Laboratory PBA, IFREMER Centre Nantes, F-44311 Nantes, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Berard
authors.affiliation: IFREMER Laboratory PBA, IFREMER Centre Nantes, F-44311 Nantes, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Serive
authors.affiliation: IFREMER Laboratory PBA, IFREMER Centre Nantes, F-44311 Nantes, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Kaas
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Isabelle
authors.identifier: 0000-0002-7268-3950
authors.initials: I
authors.lastname: Lanneluc
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Thiery
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lafferriere
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Piot
authors.affiliation: Department LASER, CHU Nantes, F-44093 Nantes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Patrice
authors.affiliation: IFREMER Laboratory PBA, IFREMER Centre Nantes, F-44311 Nantes, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Cadoret
authors.affiliation: University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Picot
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D058086:Microalgae / Q000737:chemistry*; D024341:Xanthophylls / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D024341:Xanthophylls; C005613:violaxanthin