Requirement of CLIC4 Expression in Human Colorectal Cancer Cells for Sensitivity to Growth Inhibition by Fucoxanthinol.

BACKGROUND/AIM: Fucoxanthinol (FxOH), a marine carotenoid, induces apoptosis and anoikis in human colorectal cancer (CRC) DLD-1 cells via the down-regulation of chloride intracellular channel 4 (CLIC4) expression, a key molecule for apoptosis. However, whether FxOH is susceptible to CLIC4 expression and its regulatory mechanisms in human CRC cells remains unknown. We investigated the inhibitory effects of FxOH on six types of human CRC cells with CLIC4 regulation. MATERIALS AND METHODS: The association between FxOH and CLIC4 was investigated using gene knockdown, overexpression, and transcriptome analyses. RESULTS: CLIC4 expression in CRC cells was a significant factor associated with sensitivity to FxOH. CLIC4 regulates many cancer-related signals and participates in growth inhibition in FxOH-treated DLD-1 cells. Both CLIC4 knockdown and overexpression attenuated the inhibitory effects of FxOH on DLD-1 cells. CONCLUSION: Our findings suggest that the protein expression of CLIC4 and its regulating mechanisms play significant roles regarding cell death in human CRC cells by FxOH treatment. Further investigation by in vitro and in vivo models is needed to determine the effect of CLIC4.

Stabilization of CDK6 by ribosomal protein uS7, a target protein of the natural product fucoxanthinol.

Cyclins and cyclin-dependent kinases (CDKs) regulate the cell cycle, which is important for cell proliferation and development. Cyclins bind to and activate CDKs, which then drive the cell cycle. The expression of cyclins periodically changes throughout the cell cycle, while that of CDKs remains constant. To elucidate the mechanisms underlying the constant expression of CDKs, we search for compounds that alter their expression and discover that the natural product fucoxanthinol downregulates CDK2, 4, and 6 expression. We then develop a method to immobilize a compound with a hydroxyl group onto FG beads® and identify human ribosomal protein uS7 (also known as ribosomal protein S5) as the major fucoxanthinol-binding protein using the beads and mass spectrometry. The knockdown of uS7 induces G1 cell cycle arrest with the downregulation of CDK6 in colon cancer cells. CDK6, but not CDK2 or CDK4, is degraded by the depletion of uS7, and we furthermore find that uS7 directly binds to CDK6. Fucoxanthinol decreases uS7 at the protein level in colon cancer cells. By identifying the binding proteins of a natural product, the present study reveals that ribosomal protein uS7 may contribute to the constant expression of CDK6 via a direct interaction.

A Marine Carotenoid of Fucoxanthinol Accelerates the Growth of Human Pancreatic Cancer PANC-1 Cells.

Fucoxanthin and its metabolite fucoxanthinol (FxOH), highly polar xanthophylls, exert strong anticancer effects against many cancer cell types. However, the effects of Fx and FxOH on pancreatic cancer, a high mortality cancer, remain unclear. We herein investigated whether FxOH induces apoptosis in human pancreatic cancer cells. FxOH (5.0 µmol/L) significantly promoted the growth of human pancreatic cancer PANC-1 cells, but induced apoptosis in human colorectal cancer DLD-1 cells. A microarray-based gene analysis revealed that the gene sets of cell cycle, adhesion, PI3K/AKT, MAPK, NRF2, adipogenesis, TGF-ß, STAT, and Wnt signals in PANC-1 cells were markedly altered by FxOH. A western blot analysis showed that FxOH up-regulated the expression of integrin ß1 and PPARγ as well as the activation of pFAK(Tyr397), pPaxillin(Tyr31), and pAKT(Ser473) in PANC-1 cells, but exerted the opposite effects in DLD-1 cells. Moreover, the expression of FYN, a downstream target of integrin subunits, was up-regulated (7.4-fold by qPCR) in FxOH-treated PANC-1 cells. These results suggest that FxOH accelerates the growth of PANC-1 cells by up-regulating the expression of integrin ß1, FAK, Paxillin, FYN, AKT, and PPARγ.

Effect of Fucoxanthinol on Pancreatic Ductal Adenocarcinoma Cells from an N-Nitrosobis(2-oxopropyl)amine-initiated Syrian Golden Hamster Pancreatic Carcinogenesis Model.

BACKGROUND/AIM: Fucoxanthinol (FxOH) is a marine carotenoid metabolite with potent anti-cancer activity. However, little is known about the efficacy of FxOH in pancreatic cancer. In the present study, we investigated the inhibitory effect of FxOH on six types of cells cloned from N-nitrosobis(2-oxopropyl)amine (BOP)-induced hamster pancreatic cancer (HaPC) cells. MATERIALS AND METHODS: FxOH action and its molecular mechanisms were investigated in HaPC cells using flow-cytometry, comprehensive gene array, and western blotting analyses. RESULTS: FxOH (5.0 µM) significantly suppressed the growth of four out of six types of HaPC cells. Moreover, FxOH significantly suppressed cell cycle, chemokine, integrin, actin polymerization, microtubule organization and PI3K/AKT and TGF-ß signals, and activated caspase-3 followed by apoptosis and anoikis induction in HaPC-5 cells. CONCLUSION: FxOH may have a high potential as a cancer chemopreventive agent in a hamster pancreatic carcinogenesis model.

Effects of CLIC4 on Fucoxanthinol-Induced Apoptosis in Human Colorectal Cancer Cells.

Fucoxanthin is a marine xanthophyll found in edible brown algae, and a metabolite, fucoxanthinol (FxOH), possesses a potent apoptosis inducing effect in many cancer cells. Chloride intracellular channel 4 (CLIC4) is a member of the CLIC family that plays an important role in cancer development and apoptosis. However, the role of CLIC4 in FxOH-induced apoptosis is not well understood. In this study, we investigated whether CLIC4 affects the apoptotic properties of FxOH in human colorectal cancer (CRC) cells under FxOH treatment. Treating human CRC DLD-1 cells with 5.0 µmol/L FxOH significantly induced apoptosis. FxOH downregulated CLIC4, integrin ß1, NHERF2 and pSmad2 (Ser465/467) by 0.6-, 0.7-, 0.7-, and 0.5-fold, respectively, compared with control cells without alteration of Rab35 expression. No colocalizing change was observed in CLIC4-related proteins in either control or FxOH-treated cells. CLIC4 knockdown suppressed cell growth and apoptosis. Interestingly, apoptosis induction by FxOH almost disappeared with CLIC4 knockdown. Our findings suggested that CLIC4 could be involved in FxOH-induced apoptosis in human CRC.

A Fucoxanthinol Induces Apoptosis in a Pancreatic Intraepithelial Neoplasia Cell.

BACKGROUND/AIM: Fucoxanthinol (FxOH), a predominant metabolite from fucoxanthin (Fx), can exert potential anti-cancer effects in various cancers. However, limited data are available on the effect of FxOH or Fx on pancreatic cancer. The present study investigated the effect of FxOH on a cell line derived from pancreatic cancer tissue developed in Ptf1aCre/+; LSL-k-rasG12D/+ mice. MATERIALS AND METHODS: Using flow-cytometric, microarrays, and western blotting analyses, alterations in FxOH-induced apoptosis-related gene expression and protein levels were evaluated in a mice pancreatic cancer cell line, KMPC44. RESULTS: FxOH significantly arrested the cells at S phase along with suppression of many gene sets, such as cytokine- cytokine receptor interaction and cell adhesion molecule CAMS. Moreover, attenuated protein levels for cytokine receptors, adhesion, phosphatidylinositol-3 kinase/protein kinase B, and mitogen-activated protein kinase were observed. CONCLUSION: FxOH may prevent pancreatic cancer development in a murine cancer model.

Nutraceutical characteristics of the brown seaweed carotenoid fucoxanthin.

Fucoxanthin (Fx), a major carotenoid found in brown seaweed, is known to show a unique and wide variety of biological activities. Upon absorption, Fx is metabolized to fucoxanthinol and amarouciaxanthin, and these metabolites mainly accumulate in visceral white adipose tissue (WAT). As seen in other carotenoids, Fx can quench singlet oxygen and scavenge a wide range of free radicals. The antioxidant activity is related to the neuroprotective, photoprotective, and hepatoprotective effects of Fx. Fx is also reported to show anti-cancer activity through the regulation of several biomolecules and signaling pathways that are involved in either cell cycle arrest, apoptosis, or metastasis suppression. Among the biological activities of Fx, anti-obesity is the most well-studied and most promising effect. This effect is primarily based on the upregulation of thermogenesis by uncoupling protein 1 expression and the increase in the metabolic rate induced by mitochondrial activation. In addition, Fx shows anti-diabetic effects by improving insulin resistance and promoting glucose utilization in skeletal muscle.

Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway.

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA-PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1ß, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway.

Fucoxanthinol attenuates oxidative stress-induced atrophy and loss in myotubes and reduces the triacylglycerol content in mature adipocytes.

The combination of sarcopenia and obesity (i.e., sarcopenic obesity) is more strongly associated with disability and metabolic/cardiovascular diseases than obesity or sarcopenia alone. Therefore, countermeasures that simultaneously suppress fat gain and muscle atrophy to prevent an increase in sarcopenic obesity are warranted. The aim of this study was to investigate the simultaneous effects of fucoxanthinol (FXOH) on fat loss in mature adipocytes and the inhibition of atrophy and loss in myotubes induced by oxidative stress. C2C12 myotubes were treated with FXOH for 24 h and further incubated with hydrogen peroxide (H2O2) for 24 h. The area of myosin heavy chain-positive myotubes and the ROS concentration were measured. Mature 3T3-L1 adipocytes were treated with FXOH for 72 h. The triacylglycerol (TG) content and glycerol and fatty acid (FA) release were biochemically measured. The myotube area was smaller in H2O2-treated cells than that in control cells. However, FXOH protected against the H2O2-induced decreases in myotube area. Further, the ROS concentration was significantly higher in the FXOH-treated cells compared with that in the control cells, although it was significantly lower than that in the H2O2-treated cells. On the other hand, in the mature adipocytes, the TG content was significantly decreased by FXOH treatment compared to that in the control. Moreover, FXOH treatment significantly increased glycerol and FA release compared with that of the control. These results suggest that FXOH inhibits H2O2-induced atrophy and loss in myotubes and activates lipolysis and decreases the TG content in mature adipocytes. Accordingly, FXOH has the potential to exert anti-sarcopenic obesity effects.

Fucoxanthinol from the Diatom Nitzschia Laevis Ameliorates Neuroinflammatory Responses in Lipopolysaccharide-Stimulated BV-2 Microglia.

In recent years, microalgae have drawn increasing attention as a valuable source of functional food ingredients. Intriguingly, Nitzschia laevis is rich in fucoxanthinol that is seldom found in natural sources. Fucoxanthinol, a marine xanthophyll carotenoid, possesses various beneficial bioactivities. Nevertheless, it's not clear whether fucoxanthinol could exert anti-neuroinflammatory function. In light of these premises, the aim of the present study was to investigate the anti-inflammatory role of fucoxanthinol purified from Nitzschia laevis in Lipopolysaccharide (LPS)-stimulated microglia. The results showed that pre-treatment of fucoxanthinol remarkably attenuated the expression of LPS-induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the production of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE-2), nitric oxide (NO) and reactive oxygen species (ROS) induction. Modulation mechanism studies revealed that fucoxanthinol hampered nuclear factor-kappa B (NF-κB), Akt, and mitogen-activated protein kinase (MAPK) pathways. Meanwhile, fucoxanthinol led to the enhancement of nuclear translocation of NF-E2-related factor 2 (Nrf2), and the upregulation of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Taken together, the results indicated that fucoxanthinol obtained from Nitzschia laevis had great potential as a neuroprotective agent in neuroinflammation and neurodegenerative disorders.

Accumulation of red apocarotenoid ß-citraurin in peel of a spontaneous mutant of huyou (Citrus changshanensis) and the effects of storage temperature and ethylene application.

Red-peeled huyou has a distinct red peel color due mainly to the presence of red apocarotenoid ß-citraurin as well as the increase in amount of total carotenoids. The expression level of carotenoid cleavage dioxygenase 4b1 (CCD4b1) accounted for 99.0% of total transcript abundance of CCD4s in red-peeled huyou peel and was nearly 100 times higher than that in ordinary huyou. ß-Citraurin accumulation and peel coloration was mostly favored at 15 °C but strongly inhibited at moderately high temperatures 20 °C and 25 °C. Exogenous ethylene application for 3 d had no obvious effect on ß-citraurin accumulation in red-peeled huyou but holding fruit at moderately higher temperatures (20 °C and 25 °C) for 3 d had a significant adverse effect on ß-citraurin accumulation. The expression of phytoene synthase 1 (PSY1) and CCD4b1 was higher at 10 °C and 15 °C and significantly lower at 20 °C and 25 °C. The mechanisms governing the accumulation of ß-citraurin are discussed.

Oleic acid as a protein ligand improving intestinal absorption and ocular benefit of fucoxanthin in water through protein-based encapsulation.

In this work, fucoxanthin-oleic acid-protein complexes were constructed to improve the dispersibility and intestinal absorption of fucoxanthin in water. The in vivo absorption/antioxidant capacity was evaluated using a mouse model, and the binding processes were investigated using multi-spectroscopic methods and molecular docking. Results showed that the oleic acid-protein delivery system dramatically improved the absorption of fucoxanthin mainly in its original form. When the molar ratio of oleic acid to bovine serum albumin (BSA) was 4 : 1, the plasma response level of fucoxanthin at 4 h could reach 91.25% that of the pure soybean oil delivery system (336.9 pg mL-1vs. 369.2 pmol mL-1). Furthermore, the loading capacity of BSA to fucoxanthin was increased 5 times when oleic acid acted as a protein ligand. Fucoxanthin, oleic acid and BSA can form complexes with good water dispersibility (transmittance nearly 90% and particle size 265 nm) at the molar ratio of 5 : 4 : 1. Spectral analysis and molecular docking indicated that oleic acid and fucoxanthin have different binding domains in BSA and that fucoxanthin can bind to the hydrophobic cavity of BSA in a static manner. After administration of fucoxanthin-oleic acid-BSA complexes for 15 days in mice, only fucoxanthinol accumulation was discovered in eyes and the ocular antioxidant capability increased by 71.02%. These results suggest that the oleic acid-protein delivery system may be useful in facilitating the application of fat-soluble active substances to hydrophilic food systems.

A novel strategy for isolation and purification of fucoxanthinol and fucoxanthin from the diatom Nitzschia laevis.

In this study, the microalga Nitzschia laevis (N. laevis) can accumulate a marine carotenoid fucoxanthinol. In particular, fucoxanthinol was firstly isolated from microalgae, accompanied by its derivative fucoxanthin. The identification and quantification of fucoxanthinol and fucoxanthin were determined by ultra-performance liquid chromatography coupled to photodiode array detector-quadrupole/travelling-wave ion mobility mass spectrometry/time-of-flight mass spectrometry (UPLC-PDA-TWIMS-QTOF-MS). Furthermore, a cost-effective approach mediated with solid-phase extraction (SPE) and thin-layer chromatography (TLC) technique was used to isolate and purify fucoxanthinol and fucoxanthin from the extracts of N. laevis. This two-step method can obtain 98% fucoxanthinol and 95% fucoxanthin, with the recovery efficiencies of around 85% for fucoxanthinol and 70% for fucoxanthin, respectively. Moreover, 1H and 13C nuclear magnetic resonance (NMR) techniques were adopted to record the purified compounds for supporting the above results. In all, the developed method has a promising potential to purify fucoxanthinol and fucoxanthin of microalgae for food and pharmaceutical applications.

Determination of fucoxanthinol in rat plasma by liquid chromatography-tandem mass spectrometry.

Previous studies have indicated that dietary fucoxanthin is mainly converted into fucoxanthinol (the deacetylated form) in mammals, but the pharmacokinetics of fucoxanthinol remains unknown. In this study, after intravenous (i.v.) and intragastric gavage (i.g.) administration of fucoxanthinol to rats at 0.8 and 20 mg/kg respectively, one-step protein precipitation with methanol was employed to prepared plasma samples, and an accurate and precise liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed to determine fucoxanthinol. Plasma samples were resolved by LC-MS/MS on a reverse-phase SB-C18 column equilibrated and eluted with acetonitrile (A, 0.1% formic acid) and water (B, 0.1% formic acid) (A:B = 92:8, v/v) at a flow rate of 0.5 mL/min and the injection volume was 5 µL. Analytes were monitored by Selected-reaction monitoring in positive electrospray ionization mode. The calibration curves for fucoxanthinol were linear over the range 1.17-300 ng/mL. The inter-day and intra-day accuracy and precision were within 1.55%-7.90%. The method was applied successfully in a pharmacokinetic study of fucoxanthinol and the resulting bioavailability was calculated.

Apoptosis induction in cancer cell lines by the carotenoid Fucoxanthinol from Pseudomonas stutzeri JGI 52.

CONTEXT: Microorganisms produce a variety of pigments and many pigments from bacteria were reported to have therapeutic potential including anticancer effects. AIM: The aim of this study is to evaluate the anticancer potential a yellow pigment from newly isolated Pseudomonas stutzeri JGI 52. MATERIALS AND METHODS: Serial dilution method was adopted for the isolation of pigmented bacteria from soil sources. Pigment extraction was carried out from bacterial isolates using methanol as the solvent and the pigment was purified by thin layer chromatography. Through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the effect of the pigment fraction on cancer cells was analyzed. Apoptosis induction was evaluated by caspase-3 activity assay, DNA fragmentation analysis, cell morphology observation by AO-EB staining under the fluorescence microscope, and cellular cytotoxicity was analysed by lactate dehydrogenase (LDH) release assay. Characterization of the purified pigment was by high-performance liquid chromatography and electrospray ionization-mass spectrometry analysis. STATISTICAL ANALYSIS: Significance of the results was confirmed by performing one-way analysis of variance. RESULTS: The pigment (PY3) from P. stutzeri inhibited the proliferation of HeLa, HepG2, and Jurkat cells and found to be less toxic to lymphocytes and CHO cells. PY3 exhibited apoptotic potential in the cancer cell lines, as evidenced by cleavage of DNA, LDH release, activation of caspase-3, and decrease in cell count. Results of mass spectra indicated the presence of "fucoxanthinol" which was earlier reported as an anticancer compound from seaweeds. CONCLUSIONS: This study revealed that the pigment PY3 from P. stutzeri has anticancer potential and induced cell death by apoptosis. It was found to have the carotenoid fucoxanthinol, responsible for its observed anticancer activity.

Glycine and succinic acid are effective indicators of the suppression of epithelial-mesenchymal transition by fucoxanthinol in colorectal cancer stem-like cells.

Fucoxanthinol (FxOH) is a strong anticancer metabolite of fucoxanthin that accumulates in abundance in edible brown algae and promises human health benefits. FxOH has been shown to suppress tumorigenicity and sphere formation in human colorectal cancer stem cell (CCSC)-like spheroids (colonospheres, Csps). In the present study, we aimed to clarify the inhibitory activity of FxOH on epithelial-mesenchymal transition (EMT), which is essential for cancer recurrence and distant metastasis, and to identify intracellular low-molecular-weight metabolites that may be useful for evaluating the cellular effects of FxOH on CCSCs. FxOH significantly suppressed sphere-forming activity, migration and invasion in a dose-dependent manner. In addition, treatment with 50 µmol/l FxOH suppressed N-cadherin and vimentin expression and the activation of integrin signaling linked to EMT suppression by western blot analysis. MAPK signaling and STAT signaling related to cell growth and apoptosis in Csps derived from human CRC HT-29 and HCT116 cells were also altered. According to our metabolite profiling by GC-MS analysis, reduced glycine and succinic acid levels were correlated with EMT suppression and apoptosis induction in Csps. Our data indicate that simple amino acids such as glycine and succinic acid may be good prognostic indicators of physiological changes to CCSCs induced by FxOH treatment.

Fucoxanthin bioavailability from fucoxanthin-fortified milk: In vivo and in vitro study.

Our previous study reported the improved stability of fucoxanthin (FX) fortified in whole milk (WM) and skimmed milk (SM). In this study, in vivo and in vitro FX bioavailability were investigated using FX-fortified milk (FX-SM and FX-WM) and microalga Phaeodactylum tricornutum biomass (Pt-powder). Organ tissue accumulation of FX and its metabolites (FXOH: fucoxanthinol, AXA: amarouciaxanthin A) after repeated oral administration was in the following order: FX-SM > FX-WM > Pt-powder. In vivo pharmacokinetic study with a single oral administration also demonstrated that the absorption of FXOH and AXA was the highest for FX-SM. To reinforce the in vivo results, in vitro-simulated digestion and Caco-2 cell uptake assays were performed, which revealed that FX-SM showed the highest FX bioaccessibility (release from food matrices) and cellular uptake efficiency of FX and FXOH. In conclusion, skimmed milk was validated as an excellent food matrix for FX application in terms of stability and bioavailability.

Glycine Is a Predictor for a Suppressive Effect of Fucoxanthinol on Colonosphere Formation Under Hypoxia.

BACKGROUND/AIM: Fucoxanthinol (FxOH), a metabolite of fucoxanthin, is known to inhibit tumorigenicity of human colorectal cancer stem cells (CCSCs) and their sphere formation. Hypoxic conditions and hypoxia-inducible factors (HIFs) are essential to maintain the stemness of CCSCs. We investigated effects of FxOH on sphere formation, intercellular energy metabolites in colonospheres formed from human colorectal HT-29 cells under hypoxic conditions. RESULTS: FxOH at 50 µM suppressed HIF1α expression and activation of integrin, mitogen-activated protein kinase (MAPK), Wingless/integrated (WNT) and signal transducer and activator of transcription (STAT) signals. Moreover, expression of epithelial-mesenchymal transition- and apoptosis-related proteins in the colonospheres was lowered by FxOH. The level of glycine was reduced in hypoxic colonospheres under FxOH treatment. CONCLUSION: FxOH attenuated the sphere formation of hypoxic colonospheres, in part, by suppressing HIF1α expression. Glycine could be a potential predictor for the activity of agents that inhibit sphere formation by hypoxic colonospheres.

Vibrational relaxation dynamics of ß-carotene and its derivatives with substituents on terminal rings in electronically excited states as studied by femtosecond time-resolved stimulated Raman spectroscopy in the near-IR region.

The electronic and vibrational relaxation of carotenoids is one of the key processes in the protection of living cells as well as in the functions of proteins involved in photosynthesis. In this study, the electronic and vibrational relaxation dynamics of ß-carotene and its derivatives with substituents on the terminal rings is investigated using femtosecond time-resolved absorption and stimulated Raman spectroscopy in the near-IR region. The carbonyl substituent induces low-frequency shifts of the steady-state and transient absorption bands, decreases of the excited-state lifetimes and the acceleration of vibrational relaxation of the conjugated main chain, whereas the hydroxyl substituent only slightly affects them. The effects of the carbonyl group in the electronic relaxation dynamics are explained well by the lengthening of effective conjugation by the carbonyl group through a partial conjugation between the main chain and the terminal ring. Time-resolved near-IR stimulated Raman spectroscopy demonstrates the significance of the peripheral substitution with the carbonyl group for the vibrational energy relaxation of ß-carotene derivatives in the lowest excited singlet state.

Protective effects of fucoxanthin and fucoxanthinol against tributyltin-induced oxidative stress in HepG2 cells.

Tributyltin (TBT) is a biocide extremely toxic to a wide range of organisms, which has been used for decades for industrial purposes. Fucoxanthin is a natural carotenoid that is isolated from seaweed, and fucoxanthinol is a major primary metabolite of fucoxanthin. Although fucoxanthin and fucoxanthinol have been reported to possess anti-oxidant activities in vitro, little is known as to whether they protect against TBT-induced oxidative stress in cultured cells. In the present study, the protective effect of fucoxanthin and fucoxanthinol against oxidative stress induced by TBT was investigated. The data showed that incubation of HepG2 cells with 0.2 µM TBT significantly increased cell apoptosis, whereas treatment with fucoxanthin or fucoxanthinol (3 µM) significantly recovered cell viability. In addition, fucoxanthinol treatment significantly decreased the intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) in HepG2 cells incubated with TBT. Moreover, fucoxanthin and fucoxanthinol markedly increased the expression level of Bcl-2/Bax. These results demonstrated that both fucoxanthin and fucoxanthinol effectively prevented cytotoxicity in HepG2 cells treated with TBT, and the protective effect was likely associated with decreased intracellular ROS and MDA and increased Bcl-2/Bax levels.