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Antiproliferative Activity of Violaxanthin Isolated from Bioguided Fractionation of Dunaliella tertiolecta Extracts
University of La Rochelle, UMR CNRS 6250 LIENSs, F-17042 La Rochelle, France
IFREMER Laboratory PBA, IFREMER Centre Nantes, F-44311 Nantes, France
Department LASER, CHU Nantes, F-44093 Nantes, France
* Author to whom correspondence should be addressed.
Received: 29 March 2011; in revised form: 27 April 2011 / Accepted: 4 May 2011 / Published: 11 May 2011
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.
Keywords: pigments; microalgae; Dunaliella; violaxanthin; carotenoid; cancer; apoptosis
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Pasquet, V.; Morisset, P.; Ihammouine, S.; Chepied, A.; Aumailley, L.; Berard, J.-B.; Serive, B.; Kaas, R.; Lanneluc, I.; Thiery, V.; Lafferriere, M.; Piot, J.-M.; Patrice, T.; Cadoret, J.-P.; Picot, L. Antiproliferative Activity of Violaxanthin Isolated from Bioguided Fractionation of Dunaliella tertiolecta Extracts. Mar. Drugs 2011, 9, 819-831.
Pasquet V, Morisset P, Ihammouine S, Chepied A, Aumailley L, Berard J-B, Serive B, Kaas R, Lanneluc I, Thiery V, Lafferriere M, Piot J-M, Patrice T, Cadoret J-P, Picot L. Antiproliferative Activity of Violaxanthin Isolated from Bioguided Fractionation of Dunaliella tertiolecta Extracts. Marine Drugs. 2011; 9(5):819-831.
Pasquet, Virginie; Morisset, Perrine; Ihammouine, Said; Chepied, Amandine; Aumailley, Lucie; Berard, Jean-Baptiste; Serive, Benoit; Kaas, Raymond; Lanneluc, Isabelle; Thiery, Valerie; Lafferriere, Mathieu; Piot, Jean-Marie; Patrice, Thierry; Cadoret, Jean-Paul; Picot, Laurent. 2011. "Antiproliferative Activity of Violaxanthin Isolated from Bioguided Fractionation of Dunaliella tertiolecta Extracts." Mar. Drugs 9, no. 5: 819-831.