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PloS One 2024Hair loss/thinning is a common side effect of tamoxifen in estrogen receptor (ER) positive breast cancer therapy. Some nutraceuticals known to promote hair growth are...
BACKGROUND
Hair loss/thinning is a common side effect of tamoxifen in estrogen receptor (ER) positive breast cancer therapy. Some nutraceuticals known to promote hair growth are avoided during breast cancer therapy for fear of phytoestrogenic activity. However, not all botanical ingredients have similarities to estrogens, and in fact, no information exists as to the true interaction of these ingredients with tamoxifen. Therefore, this study sought to ascertain the effect of nutraceuticals (+/- estrogen/tamoxifen), on proliferation of breast cancer cells and the relative expression of ERα/β.
METHODS
Kelp, Astaxanthin, Saw Palmetto, Tocotrienols, Maca, Horsetail, Resveratrol, Curcumin and Ashwagandha were assessed on proliferation of MCF7, T47D and BT483 breast cancer cell lines +/- 17β-estradiol and tamoxifen. Each extract was analysed by high performance liquid chromatography (HPLC) prior to use. Cellular ERα and ERβ expression was assessed by qRT-PCR and western blot. Changes in the cellular localisation of ERα:ERβ and their ratio following incubation with the nutraceuticals was confirmed by immunocytochemistry.
RESULTS
Estradiol stimulated DNA synthesis in three different breast cancer cell lines: MCF7, T47D and BT483, which was inhibited by tamoxifen; this was mirrored by a specific ERa agonist in T47D and BT483 cells. Overall, nutraceuticals did not interfere with tamoxifen inhibition of estrogen; some even induced further inhibition when combined with tamoxifen. The ERα:ERβ ratio was higher at mRNA and protein level in all cell lines. However, incubation with nutraceuticals induced a shift to higher ERβ expression and a localization of ERs around the nuclear periphery.
CONCLUSIONS
As ERα is the key driver of estrogen-dependent breast cancer, if nutraceuticals have a higher affinity for ERβ they may offer a protective effect, particularly if they synergize and augment the actions of tamoxifen. Since ERβ is the predominant ER in the hair follicle, further studies confirming whether nutraceuticals can shift the ratio towards ERβ in hair follicle cells would support a role for them in hair growth. Although more research is needed to assess safety and efficacy, this promising data suggests the potential of nutraceuticals as adjuvant therapy for hair loss in breast cancer patients receiving endocrine therapy.
Topics: Humans; Female; Tamoxifen; Breast Neoplasms; Estrogen Receptor alpha; Estrogen Receptor beta; Estradiol; Estrogens; MCF-7 Cells; Dietary Supplements; Alopecia; Hair; Cell Line, Tumor; Cell Proliferation
PubMed: 38408073
DOI: 10.1371/journal.pone.0297080 -
Microorganisms Feb 2024Carotenoids, biotechnologically significant pigments, play crucial biological roles in marine microorganisms. While various environments have been explored to understand...
Carotenoids, biotechnologically significant pigments, play crucial biological roles in marine microorganisms. While various environments have been explored to understand the diversity of carotenoids and their biosynthesis, the Antarctic Ocean remains relatively under-investigated. This study conducted a metagenomic analysis of seawater from two depths (16 and 25 m) near the King Sejong Station in the Antarctic Ocean. The analysis revealed a rich genetic diversity underlying C40 (astaxanthin, myxol, okenone, spheroidene, and spirilloxanthin), C30 (diaponeurosporene, diapolycopene, and staphyloxanthin), and C50 (C.p. 450) carotenoid biosynthesis in marine microorganisms, with notable differential gene abundances between depth locations. Exploring carotenoid pathway genes offers the potential for discovering diverse carotenoid structures of biotechnological value and better understanding their roles in individual microorganisms and broader ecosystems.
PubMed: 38399795
DOI: 10.3390/microorganisms12020390 -
Microorganisms Feb 2024Canthaxanthin is an important antioxidant with wide application prospects, and β-carotene ketolase is the key enzyme involved in the biosynthesis of canthaxanthin....
Canthaxanthin is an important antioxidant with wide application prospects, and β-carotene ketolase is the key enzyme involved in the biosynthesis of canthaxanthin. However, the challenge for the soluble expression of β-carotene ketolase is that it hinders the large-scale production of carotenoids such as canthaxanthin and astaxanthin. Hence, this study employed several strategies aiming to improve the soluble expression of β-carotene ketolase and its activity, including selecting optimal expression vectors, screening induction temperatures, adding soluble expression tags, and adding a molecular chaperone. Results showed that all these strategies can improve the soluble expression and activity of β-carotene ketolase in . In particular, the production of soluble β-carotene ketolase was increased 8 times, with a commercial molecular chaperon of pG-KJE8, leading to a 1.16-fold enhancement in the canthaxanthin production from β-carotene. Interestingly, pG-KJE8 could also enhance the soluble expression of β-carotene ketolase derived from eukaryotic microalgae. Further research showed that the production of canthaxanthin and echinenone was significantly improved by as many as 30.77 times when the pG-KJE8 was added, indicating the molecular chaperone performed differently among different β-carotene ketolase. This study not only laid a foundation for further research on the improvement of β-carotene ketolase activity but also provided new ideas for the improvement of carotenoid production.
PubMed: 38399781
DOI: 10.3390/microorganisms12020377 -
Foods (Basel, Switzerland) Feb 2024Obesity has become a serious global public health risk threatening millions of people. In this study, the astaxanthin-anthocyanin nanoparticles (AXT-ACN NPs) were used...
Obesity has become a serious global public health risk threatening millions of people. In this study, the astaxanthin-anthocyanin nanoparticles (AXT-ACN NPs) were used to investigate their effects on the lipid accumulation and antioxidative capacity of the high-sugar-diet-induced high-fat (). It can be found that the lifespan, motility, and reproductive capacity of the high-fat were significantly decreased compared to the normal nematodes in the control group. However, treatment of high-fat with AXT-ACN NPs resulted in a prolonged lifespan of 35 days, improved motility, and a 22.06% increase in total spawn production of the nematodes. Furthermore, AXT-ACN NPs were found to effectively extend the lifespan of high-fat under heat and oxidative stress conditions. Oil-red O staining results also demonstrated that AXT-ACN NPs have a remarkable effect on reducing the fat accumulation in nematodes, compared with pure astaxanthin and anthocyanin nanoparticles. Additionally, AXT-ACN NPs can significantly decrease the accumulation of lipofuscin and the level of reactive oxygen species (ROS). The activities of antioxidant-related enzymes in nematodes were further measured, which revealed that the AXT-ACN NPs could increase the activities of catalase (CAT), superoxidase dismutase (SOD), and glutathione peroxidase (GSH-Px), and decrease the malondialdehyde (MDA) content. The astaxanthin and anthocyanin in AXT-ACN NPs showed sound synergistic antioxidation and lipid-lowering effects, making them potential components in functional foods.
PubMed: 38397491
DOI: 10.3390/foods13040514 -
Toxins Jan 2024Ochratoxin A (OTA), a common mycotoxin, can contaminate food and feed and is difficult to remove. Astaxanthin (ASTA), a natural antioxidant, can effectively protect...
Ochratoxin A (OTA), a common mycotoxin, can contaminate food and feed and is difficult to remove. Astaxanthin (ASTA), a natural antioxidant, can effectively protect against OTA-induced hepatotoxicity; however, its mechanism of action remains unclear. In the present study, we elucidate the protective effects of ASTA on the OTA-induced damage of the endoplasmic reticulum and mitochondria in broiler liver samples by serum biochemical analysis, antioxidant analysis, qRT-PCR, and Western blot analysis. ASTA inhibited the expressions of , , , , , , , and genes, and significantly alleviated OTA-induced liver oxidative damage (SOD, GSH-Px, GSH, MDA). Furthermore, it inhibited OTA-activated endoplasmic reticulum stress genes and proteins (, GRP78, , ATF6, , , , CHOP). ASTA alleviated OTA-induced mitochondrial dynamic imbalance, inhibited mitochondrial division (DRP1, ), and promoted mitochondrial fusion (OPA1, MFN1, MFN2). In conclusion, ASTA can decrease OTA-induced oxidative damage, thereby alleviating endoplasmic reticulum stress and mitochondrial dynamic imbalance.
Topics: Animals; Antioxidants; Mitochondrial Dynamics; Chemical and Drug Induced Liver Injury, Chronic; Chickens; Oxidative Stress; Liver Diseases; Endoplasmic Reticulum Stress; Apoptosis; Ochratoxins; Xanthophylls
PubMed: 38393146
DOI: 10.3390/toxins16020068 -
Marine Drugs Jan 2024Oxidative stress, which damages cellular components and causes mitochondrial dysfunction, occurs in a variety of human diseases, including neurological disorders. The...
Oxidative stress, which damages cellular components and causes mitochondrial dysfunction, occurs in a variety of human diseases, including neurological disorders. The clearance of damaged mitochondria via mitophagy maintains the normal function of mitochondria and facilitates cell survival. Astaxanthin is an antioxidant known to have neuroprotective effects, but the underlying mechanisms remain unclear. This study demonstrated that astaxanthin inhibited HO-induced apoptosis in SH-SY5Y cells by ameliorating mitochondrial damage and enhancing cell survival. HO treatment significantly reduced the levels of activated Akt and mTOR and induced mitophagy, while pretreatment with astaxanthin prevented HO-induced inhibition of Akt and mTOR and attenuated HO-induced mitophagy. Moreover, the inhibition of Akt attenuated the protective effect of astaxanthin against HO-induced cytotoxicity. Taken together, astaxanthin might inhibit HO-induced apoptosis by protecting mitochondrial function and reducing mitophagy. The results also indicate that the Akt/mTOR signaling pathway was critical for the protection of astaxanthin against HO-induced cytotoxicity. The results from the present study suggest that astaxanthin can reduce neuronal oxidative injury and may have the potential to be used for preventing neurotoxicity associated with neurodegenerative diseases.
Topics: Humans; Proto-Oncogene Proteins c-akt; Hydrogen Peroxide; Mitophagy; Neuroblastoma; Apoptosis; Oxidative Stress; TOR Serine-Threonine Kinases; Cell Line, Tumor; Reactive Oxygen Species; Xanthophylls
PubMed: 38393028
DOI: 10.3390/md22020057 -
Biochemical Society Transactions Feb 2024Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the pro-oxidant state is a result of increased production of reactive oxygen species... (Review)
Review
Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the pro-oxidant state is a result of increased production of reactive oxygen species (ROS) or inadequate antioxidant protection. ROS are produced through several mechanisms in cells including during mitochondrial oxidative phosphorylation. Increased mitochondrial-derived ROS are associated with mitochondrial dysfunction, an early event in age-related diseases such as Alzheimer's diseases (ADs) and in metabolic disorders including diabetes. AD post-mortem investigations of affected brain regions have shown the accumulation of oxidative damage to macromolecules, and oxidative stress has been considered an important contributor to disease pathology. An increase in oxidative stress, which leads to increased levels of superoxide, hydrogen peroxide and other ROS in a potentially vicious cycle is both causative and a consequence of mitochondrial dysfunction. Mitochondrial dysfunction may be ameliorated by molecules with antioxidant capacities that accumulate in mitochondria such as carotenoids. However, the role of carotenoids in mitigating mitochondrial dysfunction is not fully understood. A better understanding of the role of antioxidants in mitochondrial function is a promising lead towards the development of novel and effective treatment strategies for age-related diseases. This review evaluates and summarises some of the latest developments and insights into the effects of carotenoids on mitochondrial dysfunction with a focus on the antioxidant properties of carotenoids. The mitochondria-protective role of carotenoids may be key in therapeutic strategies and targeting the mitochondria ROS is emerging in drug development for age-related diseases.
Topics: Humans; Antioxidants; Reactive Oxygen Species; Carotenoids; Oxidative Stress; Mitochondrial Diseases
PubMed: 38385583
DOI: 10.1042/BST20230193 -
Nature Communications Feb 2024Microbes are increasingly employed as cell factories to produce biomolecules. This often involves the expression of complex heterologous biosynthesis pathways in host...
Microbes are increasingly employed as cell factories to produce biomolecules. This often involves the expression of complex heterologous biosynthesis pathways in host strains. Achieving maximal product yields and avoiding build-up of (toxic) intermediates requires balanced expression of every pathway gene. However, despite progress in metabolic modeling, the optimization of gene expression still heavily relies on trial-and-error. Here, we report an approach for in vivo, multiplexed Gene Expression Modification by LoxPsym-Cre Recombination (GEMbLeR). GEMbLeR exploits orthogonal LoxPsym sites to independently shuffle promoter and terminator modules at distinct genomic loci. This approach facilitates creation of large strain libraries, in which expression of every pathway gene ranges over 120-fold and each strain harbors a unique expression profile. When applied to the biosynthetic pathway of astaxanthin, an industrially relevant antioxidant, a single round of GEMbLeR improved pathway flux and doubled production titers. Together, this shows that GEMbLeR allows rapid and efficient gene expression optimization in heterologous biosynthetic pathways, offering possibilities for enhancing the performance of microbial cell factories.
Topics: Saccharomyces cerevisiae; Recombinases; Biosynthetic Pathways; Gene Editing; Gene Expression; Metabolic Engineering
PubMed: 38326309
DOI: 10.1038/s41467-024-44997-7 -
Journal of Oleo Science 2024The effects of microwave drying conditions of a Paracoccus carotinifaciens culture solution on astaxanthin Z-isomerization and degradation were investigated. The...
The effects of microwave drying conditions of a Paracoccus carotinifaciens culture solution on astaxanthin Z-isomerization and degradation were investigated. The microwave drying significantly increase the ratio of astaxanthin Z-isomers, and the higher the microwave power and the longer the drying time, the higher the total Z-isomer ratio of astaxanthin, but such conditions also accelerated astaxanthin degradation. We found that the addition of powdered oils enhanced the Z-isomerization reaction. For example, when the P. carotinifaciens culture solution was dried at 1000 W power for 5 min without and with powdered rapeseed oil, total Z-isomer ratios of astaxanthin in resulting dried powder were 14.9 and 47.4%, respectively. Furthermore, the storage test of the dried P. carotinifaciens powder showed that astaxanthin Z- isomers were stable at 4℃ in a low-oxygen atmosphere. As astaxanthin Z-isomers have greater bioavailability and potentially exhibit superior biological activities than the all-E-isomer, the dried P. carotinifaciens powder obtained by the method of this study is expected to be used as a value-added astaxanthin source.
Topics: Isomerism; Microwaves; Powders; Paracoccus; Xanthophylls
PubMed: 38311406
DOI: 10.5650/jos.ess23093 -
Nature Communications Feb 2024Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory...
Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.
Topics: Female; Animals; Mice; Microalgae; Reactive Oxygen Species; Diabetes Mellitus; Diabetic Foot; Anti-Bacterial Agents; Hypoxia; Oxygen; Wound Healing; Hydrogels
PubMed: 38310127
DOI: 10.1038/s41467-024-45101-9