Fucoxanthin, a Marine Carotenoid, Attenuates <i>β</i>‐Amyloid Oligomer‐Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH‐SY5Y Cells

Lin, Jiajia; Li, Jingling; Zhao, Jichun; Zhang, Ke; Zheng, Jun; Wang, Jialing; Huang, Chunhui; Zhang, Jingrong; Yan, Xiaojun; Gerwick, William H.; Wang, Qinwen; Cui, Wei; He, Shan

doi:10.1155/2017/6792543

Cited by 73 publications

(58 citation statements)

References 38 publications

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“…S1). In agreement with earlier reports, SH-SY5Y responds mildly to the MAPK inhibitor U-0126 [22][23][24] , whereas CLB-GA responds more strongly to the PI 3 K/AKT inhibitor pictilisib. This can be explained by compensation by the alternate pathway, since it is known that the RAS/MAPK and PI 3 K/AKT pathways communicate at many nodes 25 .…”

Section: Alk Fusion Genes Upregulate Etv5 Expression In Alcl and Nsclsupporting

confidence: 93%

The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness

Mus

Lambertz

Claeys

et al. 2020

Sci Rep

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neuroblastoma is an aggressive childhood cancer arising from sympatho-adrenergic neuronal progenitors. the low survival rates for high-risk disease point to an urgent need for novel targeted therapeutic approaches. Detailed molecular characterization of the neuroblastoma genomic landscape indicates that ALK-activating mutations are present in 10% of primary tumours. Together with other mutations causing RAS/MAPK pathway activation, ALK mutations are also enriched in relapsed cases and ALK activation was shown to accelerate MYCN-driven tumour formation through hitherto unknown ALK-driven target genes. to gain further insight into how ALK contributes to neuroblastoma aggressiveness, we searched for known oncogenes in our previously reported ALK-driven gene signature. We identified ETV5, a bona fide oncogene in prostate cancer, as robustly upregulated in neuroblastoma cells harbouring ALK mutations, and show high ETV5 levels downstream of the RAS/MAPK axis. Increased ETV5 expression significantly impacted migration, invasion and colony formation in vitro, and ETV5 knockdown reduced proliferation in a murine xenograft model. We also established a gene signature associated with ETV5 knockdown that correlates with poor patient survival. Taken together, our data highlight ETV5 as an intrinsic component of oncogenic ALK-driven signalling through the MApK axis and propose that ETV5 upregulation in neuroblastoma may contribute to tumour aggressiveness. Neuroblastoma is the most common extracranial solid paediatric tumour, accounting for 15% of all childhood cancer deaths and arises from the developing sympathetic nervous system 1. In patients with high-risk disease, 5-year event-free survival is less than 50% 2 , with survivors often suffering from severe side-effects associated with current intensive multi-modal therapies and relapse after first-line therapy 1. Recent sequencing efforts have established the mutational landscape of primary and relapsed neuroblastoma. Primary neuroblastomas, similar to other embryonic tumours, have a very low mutation burden. The 'anaplastic lymphoma kinase' (ALK) tyrosine kinase receptor is the only target with significant recurrent mutations occurring in up to 10% of sporadic cases

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Section: Alk Fusion Genes Upregulate Etv5 Expression In Alcl and Nsclsupporting

confidence: 93%

The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness

Mus

Lambertz

Claeys

et al. 2020

Sci Rep

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“…In fact, fucoxanthin showed significant neuroprotection to PC-12 cells against Aβ 1-42 at all tested concentrations (0.01-2 µM) in this study (p<0.05). These results are comparable to recent studies as 1 µM of fucoxanthin demonstrated the ability to increase cell viability compromised by Aβ 1-42 in SH-SY5Y cells from 50% to almost 80% (Xiang et al, 2017), and increase cell viability from 55% to 87% comparing to control Aβ oligomer-induced toxicity in SH-SY5Y cells (Lin et al, 2017). In our study 1 µM of fucoxanthin was able to increase cell viability compromised by Aβ 1-42 from around 67% to 98.5% in PC12 cells.…”

Section: Accepted Manuscriptsupporting

confidence: 89%

“…Treating PC-12 cells with Aβ 1-42 (1 µM) for 48 hours and measuring apoptosis using fucoxanthin reduced apoptotic cells to 20% (Lin et al, 2017). This result is consistent with a report that astaxanthin inhibited apoptosis induced by H 2 O 2 in mouse neural progenitor cells (Kim et al, 2009), 6-OHDA in SH-SY5Y cells (Ikeda et al, 2008) and Aβ 25-35 in SH-SY5Y cells (Wang et al, 2010).…”

Section: Astaxanthin and Fucoxanthin Inhibited Aβ 1-42 -Induced Apoptsupporting

confidence: 86%

“…This result is consistent with a report that astaxanthin inhibited apoptosis induced by H 2 O 2 in mouse neural progenitor cells (Kim et al, 2009), 6-OHDA in SH-SY5Y cells (Ikeda et al, 2008) and Aβ 25-35 in SH-SY5Y cells (Wang et al, 2010). Similarly, fucoxanthin has been previously shown to reduce apoptosis induced by both H 2 O 2 (Yu et al, 2017) and Aβ oligomer in SH-SY5Y cells (Lin et al, 2017). These results suggested that both compounds demonstrate a pleitropic neuroprotective effect in vitro, by inhibiting overt toxicity, apoptosis and aggregation of Aβ 1-42 .…”

Section: Astaxanthin and Fucoxanthin Inhibited Aβ 1-42 -Induced Apoptmentioning

confidence: 67%

“…Fucoxanthin was found to protect SH-SY5Y cells against Aβ oligomer via inhibiting ERK pathway and activating PI3K/Akt pathway (Lin et al, 2017).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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In vitro studies of the neuroprotective activities of astaxanthin and fucoxanthin against amyloid beta (Aβ1-42) toxicity and aggregation

Alghazwi

Smid

Musgrave

et al. 2019

Neurochemistry International

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Amyloid beta (Aβ) can aggregate and form plaques, which are considered as one of the major hallmarks of Alzheimer's disease. This study aims to directly compare the neuroprotective activities in vitro of two marine-derived carotenoids astaxanthin and fucoxanthin that have shown a spectrum of biological activities, including neuroprotection. The in vitro neuroprotective activities were investigated against Aβ 1-42-mediated toxicity in pheochromocytoma (PC-12) neuronal cells using the MTT cell viability assay, anti-apoptotic, antioxidant and neurite outgrowth activities; as well as inhibition against Aβ 1-42 fibrillization in the Thioflavin T (ThT) assay of fibril kinetics and via transmission electron microscopic (TEM) evaluation of fibril morphology. The results demonstrated that both astaxanthin and fucoxanthin exhibited multineuroprotective effects favouring fucoxanthin over astaxanthin supporting neuroprotective roles of marine-derived carotenoids as potential novel dementia prevention or therapeutic strategies.

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Fucoxanthin prevents cell growth and induces apoptosis in endometrial cancer HEC‐1A cells by the inhibition of the PI3K/Akt/mTOR pathway

Sun

Yang

et al. 2022

J Biochem & Molecular Tox

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Endometrial cancer is the major type of gynecological cancer and ranks as the sixth most common cancer in women. Endometrial cancer usually is diagnosed in an advanced stage, complicating the treatments in many cases. The present research was focused on unveiling the in vitro anticancer role of fucoxanthin against the endometrial cancer HEC‐1A cells by inhibiting the phosphatidylinositol‐3‐kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling axis. The cytotoxicity of fucoxanthin against the endometrial cancer HEC‐1A cells was studied using the MTT test. The level of reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) status, and apoptotic cell death in the 7.5 and 10 µM administered HEC‐1A cells were assayed using fluorescent staining techniques. The messenger RNA expression was analyzed using RT‐PCR for PI3K/Akt/mTOR signaling molecules, proapoptotic (Bax and caspase‐3) antiapoptotic (cyclin D1 and Bcl‐2) genes, and inflammatory markers like tumour necrosis factor α (TNFα), nuclear factor kappa B (NF‐κB), Cox‐2, and interleukin (IL)‐6. The cell viability assay proved that fucoxanthin effectively prevented HEC‐1A cell viability, where the IC50 was 7.5 µM. Fucoxanthin at 7.5 and 10 µM remarkably improved ROS production and apoptosis and decreased the MMP in HEC‐1A cells. The fucoxanthin effectively inhibited the PI3K/Akt/mTOR cascade along with the expression of TNF‐α, NF‐κB, Cox‐2, and IL‐6 and antiapoptotic genes cyclin D1 and Bcl‐2 in the HEC‐1A cells. Fucoxanthin treatment also enhanced the Bax and caspase‐3 expressions in the HEC‐1A cells. Our results from this work unveiled that fucoxanthin triggered growth inhibition and apoptosis in endometrial cancer HEC‐1A cells. Besides, fucoxanthin inhibited the PI3K/Akt/mTOR cascade and improved apoptotic marker expressions in the HEC‐1A cells.

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Fucoxanthin, a Marine Carotenoid, Attenuates β‐Amyloid Oligomer‐Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH‐SY5Y Cells

Cited by 73 publications

References 38 publications

The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness

The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness

In vitro studies of the neuroprotective activities of astaxanthin and fucoxanthin against amyloid beta (Aβ1-42) toxicity and aggregation

Fucoxanthin prevents cell growth and induces apoptosis in endometrial cancer HEC‐1A cells by the inhibition of the PI3K/Akt/mTOR pathway

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