Special Issue "Marine Carotenoids in Inflammation and Cancer"

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (30 September 2021).

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A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Elena Talero
E-Mail Website
Guest Editor
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain
Interests: peptides; natural products; inflammation; inflammatory bowel disease; colon cancer; inflammatory skin diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Javier Ávila-Román
E-Mail Website
Guest Editor
Department of Biochemistry and Biotechnology, Faulty of Chemistry, Universitat Rovira i Virgili
Interests: microalgae; Inflammation; oxylipins; Inflammatory Bowel Disease; colon cancer; inflammatory skin diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute inflammation is a biological response that can arise in organisms in response to pathogens, toxic agents, or tissue damage, with the aim of removing harmful stimuli and restoring tissue homeostasis. Nevertheless, uncontrolled acute inflammation can lead to a chronic inflammatory state, which is believed to play a main role in the pathogenesis of many diseases, including cancer. In this context, an oxidative environment or the presence of reactive oxygen species (ROS) stimulate intracellular signaling pathways and transcription factors, including MAPK and NF-kB, among others. ROS can also activate a multiprotein complex called inflammasome, which regulates the activation of caspase-1 and subsequent maturation of pro-inflammatory cytokines (IL-1β and IL-18). The transcription factor Nrf2 plays a pivotal role in protection against oxidative stress in a multitude of inflammatory diseases since it regulates the transcription of antioxidant enzymes.

Currently, the need to find new anti-inflammatory and anticancer compounds has given rise to a vast number of studies in the marine environment, which represents an excellent source to isolate bioactive molecules, such as carotenoids. Carotenoids are natural isoprenoid pigments synthesized by photosynthetic organisms such as plants, protists, bacteria, heterotrophic bacteria, some fungi, and some invertebrates. In addition, carotenoids have been found in marine organisms, such as algae, and small invertebrates, including sponges, tunicates, bryozoans, and mollusks, as well as microalgae, which are a vast source of carotenoids containing up to 0.2 % of them. Animals require a dietary intake of carotenoids to meet daily health demands because they are unable to synthesize them. There are two subtypes of carotenoids, carotenes (hydrocarbon carotenoids) and xanthophylls (oxygenate derivatives), and they comprise many of the yellow, orange, and red pigments in nature. Currently, lycopene, β-carotene, canthaxanthin, zeaxanthin, astaxanthin, and fucoxanthin are synthesized on an industrial scale for food and cosmetic purposes. Moreover, many of these carotenoids are being studied as chemopreventive agents against inflammation and cancer. This Special Issue of Marine Drugs will cover the entire scope of marine carotenoids with anti-inflammatory and anticancer activities, both in vitro and in vivo, as well as the latest status of clinical development from carotenoids trials. In particular, works that evaluate the molecular mechanisms of these compounds are especially encouraged.

Prof. Elena Talero
Dr. Javier Ávila-Román
Guest Editors

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Keywords

  • Carotenoids
  • Anti-inflammatory
  • Anticancer

Published Papers (9 papers)

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Research

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Article
Gloeothece sp.—Exploiting a New Source of Antioxidant, Anti-Inflammatory, and Antitumor Agents
Mar. Drugs 2021, 19(11), 623; https://doi.org/10.3390/md19110623 - 04 Nov 2021
Viewed by 493
Abstract
Bioactive lipidic compounds of microalgae, such as polyunsaturated fatty acids (PUFA) and carotenoids, can avoid or treat oxidation-associated conditions and diseases like inflammation or cancer. This study aimed to assess the bioactive potential of lipidic extracts obtained from Gloeothece sp.–using Generally Recognized as [...] Read more.
Bioactive lipidic compounds of microalgae, such as polyunsaturated fatty acids (PUFA) and carotenoids, can avoid or treat oxidation-associated conditions and diseases like inflammation or cancer. This study aimed to assess the bioactive potential of lipidic extracts obtained from Gloeothece sp.–using Generally Recognized as Safe (GRAS) solvents like ethanol, acetone, hexane:isopropanol (3:2) (HI) and ethyl lactate. The bioactive potential of extracts was assessed in terms of antioxidant (ABTS•+, DPPH, NO and O2assays), anti-inflammatory (HRBC membrane stabilization and Cox-2 screening assay), and antitumor capacity (death by TUNEL, and anti-proliferative by BrdU incorporation assay in AGS cancer cells); while its composition was characterized in terms of carotenoids and fatty acids, by HPLC-DAD and GC-FID methods, respectively. Results revealed a chemopreventive potential of the HI extract owing to its ability to: (I) scavenge -NO radical (IC50, 1258 ± 0.353 µg·mL−1); (II) inhibit 50% of COX-2 expression at 130.2 ± 7.4 µg·mL−1; (III) protect 61.6 ± 9.2% of lysosomes from heat damage, and (IV) induce AGS cell death by 4.2-fold and avoid its proliferation up to 40% in a concentration of 23.2 ± 1.9 µg·mL−1. Hence, Gloeothece sp. extracts, namely HI, were revealed to have the potential to be used for nutraceutical purposes. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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Article
Antitumour Effects of Astaxanthin and Adonixanthin on Glioblastoma
Mar. Drugs 2020, 18(9), 474; https://doi.org/10.3390/md18090474 - 18 Sep 2020
Cited by 6 | Viewed by 1525
Abstract
Several antitumour drugs have been isolated from natural products and many clinical trials are underway to evaluate their potential. There have been numerous reports about the antitumour effects of astaxanthin against several tumours but no studies into its effects against glioblastoma. Astaxanthin is [...] Read more.
Several antitumour drugs have been isolated from natural products and many clinical trials are underway to evaluate their potential. There have been numerous reports about the antitumour effects of astaxanthin against several tumours but no studies into its effects against glioblastoma. Astaxanthin is a red pigment found in crustaceans and fish and is also synthesized in Haematococcus pluvialis; adonixanthin is an intermediate product of astaxanthin. It is known that both astaxanthin and adonixanthin possess radical scavenging activity and can confer a protective effect on several damages. In this study, we clarified the antitumour effects of astaxanthin and adonixanthin using glioblastoma models. Specifically, astaxanthin and adonixanthin showed an ability to suppress cell proliferation and migration in three types of glioblastoma cells. Furthermore, these compounds were confirmed to transfer to the brain in a murine model. In the murine orthotopic glioblastoma model, glioblastoma progression was suppressed by the oral administration of astaxanthin and adonixanthin at 10 and 30 mg/kg, respectively, for 10 days. These results suggest that both astaxanthin and adonixanthin have potential as treatments for glioblastoma. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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Article
Transcriptome Analysis of the Inhibitory Effect of Astaxanthin on Helicobacter pylori-Induced Gastric Carcinoma Cell Motility
Mar. Drugs 2020, 18(7), 365; https://doi.org/10.3390/md18070365 - 15 Jul 2020
Cited by 2 | Viewed by 1075
Abstract
Helicobacter pylori (H. pylori) infection promotes the metastasis of gastric carcinoma cells by modulating signal transduction pathways that regulate cell proliferation, motility, and invasion. Astaxanthin (ASTX), a xanthophyll carotenoid, is known to inhibit cancer cell migration and invasion, however the mechanism [...] Read more.
Helicobacter pylori (H. pylori) infection promotes the metastasis of gastric carcinoma cells by modulating signal transduction pathways that regulate cell proliferation, motility, and invasion. Astaxanthin (ASTX), a xanthophyll carotenoid, is known to inhibit cancer cell migration and invasion, however the mechanism of action of ASTX in H. pylori-infected gastric epithelial cells is not well understood. To gain insight into this process, we carried out a comparative RNA sequencing (RNA-Seq) analysis of human gastric cancer AGS (adenocarcinoma gastric) cells as a function of H. pylori infection and ASTX administration. The results were used to identify genes that are differently expressed in response to H. pylori and ASTX. Gene ontology (GO) analysis identified differentially expressed genes (DEGs) to be associated with cell cytoskeleton remodeling, motility, and/or migration. Among the 20 genes identified, those encoding c-MET, PI3KC2, PLCγ1, Cdc42, and ROCK1 were selected for verification by real-time PCR analysis. The verified genes were mapped, using signaling networks contained in the KEGG database, to create a signaling pathway through which ASTX might mitigate the effects of H. pylori-infection. We propose that H. pylori-induced upregulation of the upstream regulator c-MET, and hence, its downstream targets Cdc42 and ROCK1, is suppressed by ASTX. ASTX is also suggested to counteract H. pylori-induced activation of PI3K and PLCγ. In conclusion, ASTX can suppress H. pylori-induced gastric cancer progression by inhibiting cytoskeleton reorganization and reducing cell motility through downregulation of c-MET, EGFR, PI3KC2, PLCγ1, Cdc42, and ROCK1. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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Review

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Review
Halophilic Carotenoids and Breast Cancer: From Salt Marshes to Biomedicine
Mar. Drugs 2021, 19(11), 594; https://doi.org/10.3390/md19110594 - 21 Oct 2021
Viewed by 678
Abstract
Breast cancer is the leading cause of death among women worldwide. Over the years, oxidative stress has been linked to the onset and progression of cancer. In addition to the classical histological classification, breast carcinomas are classified into phenotypes according to hormone receptors [...] Read more.
Breast cancer is the leading cause of death among women worldwide. Over the years, oxidative stress has been linked to the onset and progression of cancer. In addition to the classical histological classification, breast carcinomas are classified into phenotypes according to hormone receptors (estrogen receptor—RE—/progesterone receptor—PR) and growth factor receptor (human epidermal growth factor receptor—HER2) expression. Luminal tumors (ER/PR-positive/HER2-negative) are present in older patients with a better outcome. However, patients with HER2-positive or triple-negative breast cancer (TNBC) (ER/PR/HER2-negative) subtypes still represent highly aggressive behavior, metastasis, poor prognosis, and drug resistance. Therefore, new alternative therapies have become an urgent clinical need. In recent years, anticancer agents based on natural products have been receiving huge interest. In particular, carotenoids are natural compounds present in fruits and vegetables, but algae, bacteria, and archaea also produce them. The antioxidant properties of carotenoids have been studied during the last years due to their potential in preventing and treating multiple diseases, including cancer. Although the effect of carotenoids on breast cancer during in vitro and in vivo studies is promising, clinical trials are still inconclusive. The haloarchaeal carotenoid bacterioruberin holds great promise to the future of biomedicine due to its particular structure, and antioxidant activity. However, much work remains to be performed to draw firm conclusions. This review summarizes the current knowledge on pre-clinical and clinical analysis on the use of carotenoids as chemopreventive and chemotherapeutic agents in breast cancer, highlighting the most recent results regarding the use of bacterioruberin from haloarchaea. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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Review
Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids
Mar. Drugs 2021, 19(10), 531; https://doi.org/10.3390/md19100531 - 23 Sep 2021
Cited by 2 | Viewed by 1032
Abstract
Acute inflammation is a key component of the immune system’s response to pathogens, toxic agents, or tissue injury, involving the stimulation of defense mechanisms aimed to removing pathogenic factors and restoring tissue homeostasis. However, uncontrolled acute inflammatory response may lead to chronic inflammation, [...] Read more.
Acute inflammation is a key component of the immune system’s response to pathogens, toxic agents, or tissue injury, involving the stimulation of defense mechanisms aimed to removing pathogenic factors and restoring tissue homeostasis. However, uncontrolled acute inflammatory response may lead to chronic inflammation, which is involved in the development of many diseases, including cancer. Nowadays, the need to find new potential therapeutic compounds has raised the worldwide scientific interest to study the marine environment. Specifically, microalgae are considered rich sources of bioactive molecules, such as carotenoids, which are natural isoprenoid pigments with important beneficial effects for health due to their biological activities. Carotenoids are essential nutrients for mammals, but they are unable to synthesize them; instead, a dietary intake of these compounds is required. Carotenoids are classified as carotenes (hydrocarbon carotenoids), such as α- and β-carotene, and xanthophylls (oxygenate derivatives) including zeaxanthin, astaxanthin, fucoxanthin, lutein, α- and β-cryptoxanthin, and canthaxanthin. This review summarizes the present up-to-date knowledge of the anti-inflammatory and anticancer activities of microalgal carotenoids both in vitro and in vivo, as well as the latest status of human studies for their potential use in prevention and treatment of inflammatory diseases and cancer. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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Review
Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent
Mar. Drugs 2021, 19(4), 201; https://doi.org/10.3390/md19040201 - 03 Apr 2021
Cited by 6 | Viewed by 1748
Abstract
Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders [...] Read more.
Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson’s disease, Alzheimer’s disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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Review
Xanthophylls from the Sea: Algae as Source of Bioactive Carotenoids
Mar. Drugs 2021, 19(4), 188; https://doi.org/10.3390/md19040188 - 27 Mar 2021
Cited by 16 | Viewed by 2118
Abstract
Algae are considered pigment-producing organisms. The function of these compounds in algae is to carry out photosynthesis. They have a great variety of pigments, which can be classified into three large groups: chlorophylls, carotenoids, and phycobilins. Within the carotenoids are xanthophylls. Xanthophylls (fucoxanthin, [...] Read more.
Algae are considered pigment-producing organisms. The function of these compounds in algae is to carry out photosynthesis. They have a great variety of pigments, which can be classified into three large groups: chlorophylls, carotenoids, and phycobilins. Within the carotenoids are xanthophylls. Xanthophylls (fucoxanthin, astaxanthin, lutein, zeaxanthin, and β-cryptoxanthin) are a type of carotenoids with anti-tumor and anti-inflammatory activities, due to their chemical structure rich in double bonds that provides them with antioxidant properties. In this context, xanthophylls can protect other molecules from oxidative stress by turning off singlet oxygen damage through various mechanisms. Based on clinical studies, this review shows the available information concerning the bioactivity and biological effects of the main xanthophylls present in algae. In addition, the algae with the highest production rate of the different compounds of interest were studied. It was observed that fucoxanthin is obtained mainly from the brown seaweeds Laminaria japonica, Undaria pinnatifida, Hizikia fusiformis, Sargassum spp., and Fucus spp. The main sources of astaxanthin are the microalgae Haematococcus pluvialis, Chlorella zofingiensis, and Chlorococcum sp. Lutein and zeaxanthin are mainly found in algal species such as Scenedesmus spp., Chlorella spp., Rhodophyta spp., or Spirulina spp. However, the extraction and purification processes of xanthophylls from algae need to be standardized to facilitate their commercialization. Finally, we assessed factors that determine the bioavailability and bioaccesibility of these molecules. We also suggested techniques that increase xanthophyll’s bioavailability. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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Review
On a Beam of Light: Photoprotective Activities of the Marine Carotenoids Astaxanthin and Fucoxanthin in Suppression of Inflammation and Cancer
Mar. Drugs 2020, 18(11), 544; https://doi.org/10.3390/md18110544 - 30 Oct 2020
Cited by 2 | Viewed by 1326
Abstract
Every day, we come into contact with ultraviolet radiation (UVR). If under medical supervision, small amounts of UVR could be beneficial, the detrimental and hazardous effects of UVR exposure dictate an unbalance towards the risks on the risk-benefit ratio. Acute and chronic effects [...] Read more.
Every day, we come into contact with ultraviolet radiation (UVR). If under medical supervision, small amounts of UVR could be beneficial, the detrimental and hazardous effects of UVR exposure dictate an unbalance towards the risks on the risk-benefit ratio. Acute and chronic effects of ultraviolet-A and ultraviolet-B involve mainly the skin, the immune system, and the eyes. Photodamage is an umbrella term that includes general phototoxicity, photoaging, and cancer caused by UVR. All these phenomena are mediated by direct or indirect oxidative stress and inflammation and are strictly connected one to the other. Astaxanthin (ASX) and fucoxanthin (FX) are peculiar marine carotenoids characterized by outstanding antioxidant properties. In particular, ASX showed exceptional efficacy in counteracting all categories of photodamages, in vitro and in vivo, thanks to both antioxidant potential and activation of alternative pathways. Less evidence has been produced about FX, but it still represents an interesting promise to prevent the detrimental effect of UVR. Altogether, these results highlight the importance of digging into the marine ecosystem to look for new compounds that could be beneficial for human health and confirm that the marine environment is as much as full of active compounds as the terrestrial one, it just needs to be more explored. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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Review
Oxidative Stress and Marine Carotenoids: Application by Using Nanoformulations
Mar. Drugs 2020, 18(8), 423; https://doi.org/10.3390/md18080423 - 13 Aug 2020
Cited by 10 | Viewed by 1888
Abstract
Carotenoids are natural fat-soluble pigments synthesized by plants, algae, fungi and microorganisms. They are responsible for the coloration of different photosynthetic organisms. Although they play a role in photosynthesis, they are also present in non-photosynthetic plant tissues, fungi, and bacteria. These metabolites have [...] Read more.
Carotenoids are natural fat-soluble pigments synthesized by plants, algae, fungi and microorganisms. They are responsible for the coloration of different photosynthetic organisms. Although they play a role in photosynthesis, they are also present in non-photosynthetic plant tissues, fungi, and bacteria. These metabolites have mainly been used in food, cosmetics, and the pharmaceutical industry. In addition to their utilization as pigmentation, they have significant therapeutically applications, such as improving immune system and preventing neurodegenerative diseases. Primarily, they have attracted attention due to their antioxidant activity. Several statistical investigations indicated an association between the use of carotenoids in diets and a decreased incidence of cancer types, suggesting the antioxidant properties of these compounds as an important factor in the scope of the studies against oxidative stress. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. Marine carotenoids (astaxanthin, fucoxanthin, β-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. Numerous of bioactive compounds such as marine carotenoids have low stability, are poorly absorbed, and own very limited bioavailability. The new technique is nanoencapsulation, which can be used to preserve marine carotenoids and their original properties during processing, storage, improve their physiochemical properties and increase their health-promoting effects. This review aims to describe the role of marine carotenoids, their potential applications and different types of advanced nanoformulations preventing and treating oxidative stress related disorders. Full article
(This article belongs to the Special Issue Marine Carotenoids in Inflammation and Cancer)
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