Astaxanthin Modulation of Signaling Pathways That Regulate Autophagy

Kim, Suhn Hyung; Kim, Hye Young

doi:10.3390/md17100546

Cited by 45 publications

(35 citation statements)

References 137 publications

(161 reference statements)

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“…AST can ameliorate cell apoptosis via more than one pathway, including ERK, NF-κB, and PI3K/Akt [27,[57][58][59]. Among these, the PI3K/Akt pathway is a prominent regulator of numerous proteins involved in cell survival through profound antioxidative and antiapoptotic actions [60].…”

Section: Discussionmentioning

confidence: 99%

Astaxanthin Protects Retinal Photoreceptor Cells against High Glucose-Induced Oxidative Stress by Induction of Antioxidant Enzymes via the PI3K/Akt/Nrf2 Pathway

Lai

Yang

2020

Antioxidants

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Diabetic retinopathy (DR) is a major microvascular complication that can lead to severe visual impairment in patients with diabetes. The elevated oxidative stress and increased reactive oxygen species (ROS) production induced by hyperglycemia have been reported to play an important role in the complex pathogenesis of DR. Astaxanthin (AST), a natural carotenoid derivative, has been recently recognized as a strong free radical scavenger and might, therefore, be beneficial in different diseases, including DR. In this study, we evaluated the potential role of AST as an antioxidative and antiapoptotic agent in protecting retinal cells and also investigated the involvement of the PI3K/Akt/Nrf2 pathway in AST-mediated effects. We treated high glucose-cultured mouse photoreceptor cells (661W) with different concentrations of AST and analyzed ROS production and cell apoptosis in the different regimens. Moreover, we also analyzed the expression of PI3K, Akt, Nrf2, and Phase II enzymes after AST treatment. Our results showed that AST dose-dependently reduced ROS production and attenuated 661W cell apoptosis in a high glucose environment. Importantly, its protective effect was abolished by treatment with PI3K or Nrf2 inhibitors, indicating the involvement of the PI3K/Akt/Nrf2 pathway. These results suggest AST as a nutritional supplement that could benefit patients with DR.

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Section: Discussionmentioning

confidence: 99%

Astaxanthin Protects Retinal Photoreceptor Cells against High Glucose-Induced Oxidative Stress by Induction of Antioxidant Enzymes via the PI3K/Akt/Nrf2 Pathway

Lai

Yang

2020

Antioxidants

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“…Recent advances in biological properties of antioxidants such as carotenoids have suggested that these compounds are not only able to prevent but also able to ameliorate diabetes and its subsequent complications [6]. In particular, astaxanthin (ASX) (3,3 -dihydroxy-β, β -carotene-4,4 -dione), a xanthophyll carotenoid [7], has been reported to exhibit multiple biological activities including modulation of OS and inflammation through free radical quenching [8] and activation of endogenous antioxidant systems via modulation of gene expression [9,10] and has numerous advantages compared to some other carotenoids. Due to its unique structure, ASX is incorporated in the lipid bilayer of cellular membranes, without damaging it, and prevents lipid-based oxidation [11].…”

Section: Introductionmentioning

confidence: 99%

Impact of Astaxanthin on Diabetes Pathogenesis and Chronic Complications

et al. 2020

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Oxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreatic β-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter endothelial cells function in both type 1 and type 2 DM. As a powerful antioxidant without side effects, astaxanthin (ASX), a xanthophyll carotenoid, has been suggested to contribute to the prevention and treatment of DM-associated pathologies. ASX reduces inflammation, OS, and apoptosis by regulating different OS pathways though the exact mechanism remains elusive. Based on several studies conducted on type 1 and type 2 DM animal models, orally or parenterally administrated ASX improves insulin resistance and insulin secretion; reduces hyperglycemia; and exerts protective effects against retinopathy, nephropathy, and neuropathy. However, more experimental support is needed to define conditions for its use. Moreover, its efficacy in diabetic patients is poorly explored. In the present review, we aimed to identify the up-to-date biological effects and underlying mechanisms of ASX on the ROS-induced DM-associated metabolic disorders and subsequent complications. The development of an in-depth research to better understand the biological mechanisms involved and to identify the most effective ASX dosage and route of administration is deemed necessary.

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“…In colorectal cancer cells, EUG was identi ed as proautophagic compound [62], where the active fraction of clove (oleanonic acid and eugenol) increased LC3B I and II and Beclin-1 protein expression. AST modulates the signaling pathways that regulate autophagy [63], either by stimulation as shown in an experimental model of non-alcoholic fatty liver disease [64], or by inhibition as shown in the pancreas by inhibiting the JAK/STAT3 pathway [65]. Also the anti-oxidant and reactive oxygen scavengining activities of EUG [66] and AST [67] during DOX treatment may explain for the classical autophagic inhibition usually observed in that context with other anti-oxidant compounds [68].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Immunomodulatory Effect of Eugenol and Astaxanthin on Doxorubicin Cytotoxicity in Hormonal Positive Breast Cancer Cells

Fouad

Sayed‐Ahmed

Huwait³

et al. 2020

Preprint

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Background: Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to improve the cytotoxic activity and reduce resistance of DOX through combination with EUG and AST in MCF7 cells.Methods: Cytotoxic activity of DOX alone and combined with either 1mM EUG or 40µM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results: DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1mM EUG or 40 µM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 µM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion: EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.

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Astaxanthin Modulation of Signaling Pathways That Regulate Autophagy

Cited by 45 publications

References 137 publications

Astaxanthin Protects Retinal Photoreceptor Cells against High Glucose-Induced Oxidative Stress by Induction of Antioxidant Enzymes via the PI3K/Akt/Nrf2 Pathway

Astaxanthin Protects Retinal Photoreceptor Cells against High Glucose-Induced Oxidative Stress by Induction of Antioxidant Enzymes via the PI3K/Akt/Nrf2 Pathway

Impact of Astaxanthin on Diabetes Pathogenesis and Chronic Complications

Epigenetic Immunomodulatory Effect of Eugenol and Astaxanthin on Doxorubicin Cytotoxicity in Hormonal Positive Breast Cancer Cells

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