Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF‐κΒ/STAT3 signalling axis in oral squamous cell carcinoma models

Kowshik, Jaganathan; Nivetha, Ramesh; Ranjani, Singaraj; Venkatesan, G. K. D. Prasanna; Selvamuthukumar, Subramanian; Veeravarmal, Veeran; Nagini, Siddavaram

doi:10.1002/iub.2104

Cited by 40 publications

(40 citation statements)

References 40 publications

(84 reference statements)

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“…This may be consistent with the known functions of microRNAs as regulators of several key tumor-related functions, including angiogenesis [23,24]. Interestingly, these data may provide evidence that miR-21 might be down-regulated among oral cancer stem cell sub-populations, a key regulator of PI3K/ Akt pathway [25,26]. These observations may be consistent with other studies that suggest control and regulation of the PI3K/STAT3/NF-kB signaling pathway may be more important to tumor functions than critical stem cell or cancer stem cell functions [27,28].…”

Section: Discussionsupporting

confidence: 78%

Differential exosome miRNA expression in oral cancer stem cells

Shoff

Booker

Leavitt

et al. 2020

ExRNA

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Background: Oral squamous cell carcinomas (OSCC) secrete exosomes into the surrounding extracellular environment to promote the horizontal transfer of bioactive molecules including microRNA (miRNA). The primary objective of this study was to explore potential differences in miRNA content between OSCC and OSCC stem cells.Methods: The OSCC cell lines SCC4, SCC15, SCC25 and CAL27 were used in these studies. The corresponding OSCC stem cells that demonstrated phenotypic adhesion independent tumor spheres (AiTS) were manually isolated. All cells were cultured in DMEM containing 10% exosome-free fetal bovine serum. Exosomes were isolated using Total Exosome Isolation reagent (Invitrogen) and RNA was purified using Total Exosome RNA isolation kit (Invitrogen). Exosome miRNA content was evaluated using miRNA Advanced Taqman Assays for miR-21, − 155, − 133, − 34, − 31, − 32, and − 365. The fold change of miRNA content was calculated using the comparative CT (ΔΔCT) method using miR-16 as an endogenous control. Results: After successful cell cultures were established, AiTS (cancer stem cells) were manually separated and confirmed using CD133 and Sox-2 biomarkers. Exosomes and extracellular vesicles were successfully isolated from all cell lines and AiTS isolates for miRNA screening. All isolates exhibited miR-16 expression (positive control), but none contained mir-31, − 32, or 133a. Differential expression of miR-21, miR-34 and miR-155 were observed with patterns observed among the cancer cell lines which were distinct from the corresponding AiTS isolates. Conclusions: Exosomes isolated from these different OSCC stem cell populations displayed nearly consistent downregulation/loss of miR-21 and miR-34 suggesting the possibility of a unique miRNA profile characteristic of oral cancer stem cells. These findings highlight the need to investigate the comprehensive functions of miR-21 and miR-34 in tumor progression and continued research to refine a miRNA profile that could aid in distinguishing tumors with poor prognosis.

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Section: Discussionsupporting

confidence: 78%

Differential exosome miRNA expression in oral cancer stem cells

Shoff

Booker

Leavitt

et al. 2020

ExRNA

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“…PI3K is an essential mediator of H. pylori -induced AGS cell migration [ 59 ]. In previous studies, ASTX treatment reduced invasive behavior of breast cancer cells and oral carcinoma cells by inhibiting PI3K signaling [ 42 , 43 ]. In a recent study carried out with oral squamous cell carcinoma models, Kowshik et al reported that ASTX inhibits hallmarks of cancer by targeting the PI3K/NF-κΒ/STAT3 signaling axis [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, ASTX treatment reduced invasive behavior of breast cancer cells and oral carcinoma cells by inhibiting PI3K signaling [ 42 , 43 ]. In a recent study carried out with oral squamous cell carcinoma models, Kowshik et al reported that ASTX inhibits hallmarks of cancer by targeting the PI3K/NF-κΒ/STAT3 signaling axis [ 43 ]. PLCγ is also an important mediator of cell migration in response to growth factor receptor activation [ 60 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, ASTX has been shown to inhibit the migration, invasion, and/or proliferation of cancerous gastric [ 36 ], liver [ 37 ], ovarian [ 38 ], breast [ 39 ], colon [ 40 ], and melanoma cells [ 41 ]. In addition, ASTX is known to target cancer-related signal transduction pathway proteins and their regulators, namely inflammatory cytokines, membrane receptors (e.g., peroxisome proliferator-activated receptor gamma (PPARγ), transcriptional regulators (e.g., NF-κB, signal transducer and activator of transcription 3 (STAT3), NF-2-related factor 2 (Nf2), and zinc finger E-box binding homeobox (ZEB)), and protein kinases (e.g., janus kinase (JAK), protein kinase B (PKB), phosphoinositide 3-kinase (PI3K) and the MAP kinases c-Jun N -terminal kinase (JNK), extracellular signal-related kinase (ERK), and p38) [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome Analysis of the Inhibitory Effect of Astaxanthin on Helicobacter pylori-Induced Gastric Carcinoma Cell Motility

Kim

2020

Marine Drugs

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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.

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“…Powerful antioxidant astaxanthin (AXT) causes inhibition of PI3K / Akt and downregulation of NF-ÿB and STAT-3 signaling pathways in an oral neoplastic cell which is demonstrated in the cell line of hamster buccal carcinogenesis model (Kowshik, 2019).…”

Section: Mechanism Of Targeted Therapy Drugs On Oral Cancermentioning

confidence: 99%

A Concise Review on Targeted Therapy for Oral Cancer

Thariny

Ezhilarasan

Brundha

2020

ijrps

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Oral Cancer has become a center of attraction in the world, causing health problems. Carcinoma that involves the lip, tongue, mouth surface, palate, and throat is also serious if not diagnosed and treated. Current treatment strategies involve surgical removal, using chemotherapeutic drugs and radiation therapy. The event of targeted therapy aid in medicine together with oral cancers is that the basic dependence of neoplasm cells on biological pathways which might be coupled to medicine that inhibit those pathways. The resistance of tumor cells to anticancer drugs is a known method which is investigated experimentally at the molecular level. Immunotherapeutic agent resistance is thought to affect the efficacy of anticancer remedies. The induced or intrinsic drug resistance has a strong effect on the survival and cancer growth prognosis by suppression of cancer-associated cell signaling pathways of cancer patients. Targeted therapy also has a significant inhibitory ability, thus demonstrating the high quality of treatment. Hence this concise review discusses the implementation of molecular targeted therapy in the treatment of oral cancer.

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Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF‐κΒ/STAT3 signalling axis in oral squamous cell carcinoma models

Cited by 40 publications

References 40 publications

Differential exosome miRNA expression in oral cancer stem cells

Differential exosome miRNA expression in oral cancer stem cells

Transcriptome Analysis of the Inhibitory Effect of Astaxanthin on Helicobacter pylori-Induced Gastric Carcinoma Cell Motility

A Concise Review on Targeted Therapy for Oral Cancer

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