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.
Highlights
Despite significant progress in prevention, diagnosis, and development during the last 25 years, cancer still represents the second cause of mortality in developed countries, after cardiovascular diseases
ML−1) of Dunaliella tertiolecta extracts on four cancer cell lines
This study unequivocally demonstrates the strong antiproliferative activity of violaxanthin on MCF-7 human mammary cancer cells grown in vitro and suggests that violaxanthin and derivatives obtained by pharmacomodulation should be studied as possible new drugs to cure breast cancer
Summary
Despite significant progress in prevention, diagnosis, and development during the last 25 years, cancer still represents the second cause of mortality in developed countries, after cardiovascular diseases. The isolation of potent anticancer molecules from the marine environment has generated interest in many groups to purify original compounds, understand their biological activity, and identify the pharmacological targets of molecules previously known for their ecological function. Bio-guided fractionation of microalgae extracts, followed by studies on human cells, has demonstrated that many pigments, beyond their ecological function as light harvesting molecules, act as potent bioactive compounds on cancer cells and may have great potential in the prevention and treatment of cancers [2]. A large number of studies have demonstrated that purified carotenoids (β,β-carotene, β,α-carotene, lutein, zeaxanthin, lycopene, fucoxanthin, astaxanthin, neoxanthin) exert a direct antiproliferative activity on cancer cells grown in vitro and induce their apoptosis [8,9,10,11,12,13,14,15]. Violaxanthin exerted a potent antiproliferative activity on MCF-7 breast cancer cells, and induced biochemical changes typical of early apoptosis
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