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Antiproliferative activity of violaxanthin isolated from bioguided fractionation of Dunaliella tertiolecta extracts.

Pasquet V, Morisset P, Ihammouine S, Chepied A, Aumailley L, Berard JB, Serive B, Kaas R, Lanneluc I, Thiery V, Lafferriere M, Piot JM, Patrice T, Cadoret JP, Picot L - Mar Drugs (2011)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: UMR CNRS 6250 LIENSs, University of La Rochelle, F-17042 La Rochelle, France.

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.

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(A) Agarose gel electrophoresis of DNA extracted from MCF-7 cells incubated for 72 h in the absence (lane –) or presence of 3,3′-Diindolylmethane 50 μM (DIM, control apoptosis inducer) (lane +); (B) Agarose gel electrophoresis of DNA extracted from MCF-7 cells treated with violaxanthin. MCF-7 cells were incubated for 72 h in the absence (lane –) or presence of violaxanthin 10 μg·mL−1 (lane 1) and 40 μg·mL−1 (lane 2).
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f8-marinedrugs-09-00819: (A) Agarose gel electrophoresis of DNA extracted from MCF-7 cells incubated for 72 h in the absence (lane –) or presence of 3,3′-Diindolylmethane 50 μM (DIM, control apoptosis inducer) (lane +); (B) Agarose gel electrophoresis of DNA extracted from MCF-7 cells treated with violaxanthin. MCF-7 cells were incubated for 72 h in the absence (lane –) or presence of violaxanthin 10 μg·mL−1 (lane 1) and 40 μg·mL−1 (lane 2).

Mentions: Violaxanthin doses evoking phosphatidylserine translocation in MCF-7 cells did not induce DNA fragmentation, even after a 72 h treatment (Figure 8B).


Antiproliferative activity of violaxanthin isolated from bioguided fractionation of Dunaliella tertiolecta extracts.

Pasquet V, Morisset P, Ihammouine S, Chepied A, Aumailley L, Berard JB, Serive B, Kaas R, Lanneluc I, Thiery V, Lafferriere M, Piot JM, Patrice T, Cadoret JP, Picot L - Mar Drugs (2011)

(A) Agarose gel electrophoresis of DNA extracted from MCF-7 cells incubated for 72 h in the absence (lane –) or presence of 3,3′-Diindolylmethane 50 μM (DIM, control apoptosis inducer) (lane +); (B) Agarose gel electrophoresis of DNA extracted from MCF-7 cells treated with violaxanthin. MCF-7 cells were incubated for 72 h in the absence (lane –) or presence of violaxanthin 10 μg·mL−1 (lane 1) and 40 μg·mL−1 (lane 2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3111184&req=5

f8-marinedrugs-09-00819: (A) Agarose gel electrophoresis of DNA extracted from MCF-7 cells incubated for 72 h in the absence (lane –) or presence of 3,3′-Diindolylmethane 50 μM (DIM, control apoptosis inducer) (lane +); (B) Agarose gel electrophoresis of DNA extracted from MCF-7 cells treated with violaxanthin. MCF-7 cells were incubated for 72 h in the absence (lane –) or presence of violaxanthin 10 μg·mL−1 (lane 1) and 40 μg·mL−1 (lane 2).
Mentions: Violaxanthin doses evoking phosphatidylserine translocation in MCF-7 cells did not induce DNA fragmentation, even after a 72 h treatment (Figure 8B).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: UMR CNRS 6250 LIENSs, University of La Rochelle, F-17042 La Rochelle, France.

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.

Show MeSH
Related in: MedlinePlus