Role and Therapeutic Targeting of the PI3K/Akt/mTOR Signaling Pathway in Skin Cancer: A Review of Current Status and Future Trends on Natural and Synthetic Agents Therapy

Cells, Год журнала: 2019, Номер 8(8), С. 803 - 803

Опубликована: Июль 31, 2019

The mammalian or mechanistic target of rapamycin (mTOR) and associated phosphatidyl-inositiol 3-kinase (PI3K)/protein kinase B (Akt) pathways regulate cell growth, differentiation, migration, survival, as well angiogenesis metabolism. Dysregulation these is frequently with genetic/epigenetic alterations predicts poor treatment outcomes in a variety human cancers including cutaneous malignancies like melanoma non-melanoma skin cancers. Recently, the enhanced understanding molecular genetic basis dysfunction patients has provided strong for development novel therapeutic strategies obdurate groups This review summarizes recent advances roles PI3K/Akt/mTOR their targets progression broad spectrum discusses current progress preclinical clinical studies targeted therapies nutraceuticals synthetic small molecule inhibitors.

Язык: Английский

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The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds

Cells, Год журнала: 2023, Номер 12(12), С. 1671 - 1671

Опубликована: Июнь 20, 2023

The dysregulated phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway has been implicated in various immune-mediated inflammatory and hyperproliferative dermatoses such as acne, atopic dermatitis, alopecia, psoriasis, wounds, vitiligo, is associated with poor treatment outcomes. Improved comprehension the consequences PI3K/Akt/mTOR patients resulted development novel therapeutic approaches. Nonetheless, more studies are necessary to validate regulatory role this create effective preventive methods for a wide range skin diseases. Several have revealed that certain natural products synthetic compounds can obstruct expression/activity PI3K/Akt/mTOR, underscoring their potential managing common persistent disorders. This review summarizes recent advances understanding activated components discusses bioactive products, scaffolds, biologic agents prevention treatment. However, further research develop therapies

Язык: Английский

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Oxidative Stress as an Important Contributor to the Pathogenesis of Psoriasis

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(17), С. 6206 - 6206

Опубликована: Авг. 27, 2020

This review discusses how oxidative stress (OS), an imbalance between oxidants and antioxidants in favor of the oxidants, increased production reactive oxygen species (ROS)/reactive nitrogen (RNS), decreased concentration/activity affect pathogenesis or cause enhancement psoriasis (Ps). Here, we also consider ROS/RNS-induced modulates activity transcriptional factors regulates numerous protein kinase cascades that participate regulation crosstalk autophagy, apoptosis, regeneration. Answers to these questions will likely uncover novel strategies for treatment Ps. Action field avoid destructive effects ROS/RNS-mediated OS resulting cellular dysfunction cell death. The combination fragmentary information on role can provide evidence extend full picture

Язык: Английский

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LncRNA MEG3 suppresses PI3K/AKT/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF-α-treated keratinocytes and psoriatic mice

Cytokine, Год журнала: 2021, Номер 148, С. 155657 - 155657

Опубликована: Авг. 20, 2021

Язык: Английский

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Rapidly dissolving microneedles for the delivery of cubosome-like liquid crystalline nanoparticles with sustained release of rapamycin

International Journal of Pharmaceutics, Год журнала: 2020, Номер 591, С. 119942 - 119942

Опубликована: Окт. 9, 2020

Язык: Английский

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Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders

Frontiers in Medicine, Год журнала: 2021, Номер 8

Опубликована: Апрель 30, 2021

PhosphoInositide-3 Kinase (PI3K) represents a family of different classes kinases which control multiple biological processes in mammalian cells, such as cell growth, proliferation, and survival. Class IA PI3Ks, the main regulators proliferative signals, consists catalytic subunit (α, β, δ) that binds p85 regulatory mediates activation AKT Target Of Rapamycin (mTOR) pathways regulation downstream effectors. Dysregulation PI3K/AKT/mTOR pathway skin contributes to several pathological conditions characterized by uncontrolled including cancers, psoriasis, atopic dermatitis (AD). Among cutaneous basal carcinoma (BCC) squamous (cSCC) display signaling hyperactivation, implicated hyperproliferation, tumorigenesis, well resistance apoptosis. Upregulation mTOR proteins has also been reported association with enhanced defective keratinocyte differentiation, senescence-like growth arrest, apoptosis, accounting for major parts overall disease phenotypes. On contrary, role AD is less characterized, even though recent evidence demonstrates relevant function epidermal barrier formation stratification. In this review, we provide most updates on molecular axis pathogenesis hyperproliferative disorders, highlights current status preclinical clinical studies PI3K-targeted therapies.

Язык: Английский

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Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1693 - 1693

Опубликована: Фев. 1, 2022

The serine/threonine kinase mechanistic target of rapamycin (mTOR) plays a pivotal role in the regulation cell proliferation, survival, and motility response to availability energy nutrients as well mitogens. mTOR signaling axis regulates important biological processes, including cellular growth, metabolism, survival many tissues. In skin, dysregulation PI3K/AKT/mTOR pathway may lead severe pathological conditions characterized by uncontrolled proliferation inflammation, skin hyperproliferative malignant diseases. Herein, we provide an update on current knowledge regarding pathogenic implication diseases with inflammatory features (such psoriasis, atopic dermatitis, pemphigus, acne) characteristics cutaneous T lymphoma melanoma) while critically discuss future perspectives for therapeutic targeting clinical practice.

Язык: Английский

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Application of microneedle patches for drug delivery; doorstep to novel therapies

Journal of Tissue Engineering, Год журнала: 2022, Номер 13

Опубликована: Янв. 1, 2022

In the past decade, microneedle-based drug delivery systems showed promising approaches to become suitable and alternative for hypodermic injections can control agent without side effects compared conventional approaches. Despite these advantages, procedure of microfabrication is facing some difficulties. For instance, loading method, stability drugs, retention time are subjects debate. Besides, application novel refining fabrication methods, types materials, instruments other issues that need further attention. Herein, we tried summarize recent achievements in controllable (microneedle patches) vitro vivo settings. addition, discussed influence delivered drugs on cellular mechanism immunization molecular signaling pathways through intradermal route. Understanding putative efficiency microneedle patches human medicine help us develop design sophisticated therapeutic modalities.

Язык: Английский

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Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation

Frontiers in Immunology, Год журнала: 2023, Номер 13

Опубликована: Янв. 18, 2023

Psoriasis is a chronic autoimmune inflammatory skin disorder characterized by epidermal hyperplasia and aberrant immune response. In addition to cytokine production, psoriasis associated with activation of the Akt/mTOR pathway. mTOR/S6K1 regulates T-lymphocyte migration, keratinocytes proliferation upregulated in psoriatic lesions. Several drugs that target Th1/Th17 cytokines or their receptors have been approved for treating humans variable results necessitating improved therapies. Fisetin, natural dietary polyphenol anti-oxidant anti-proliferative properties, covalently binds mTOR/S6K1. The effects fisetin on its underlying mechanisms not clearly defined. Here, we evaluated immunomodulatory Th1/Th17-cytokine-activated adult human (HEKa) anti-CD3/CD28-stimulated CD4 + T cells compared these activities those rapamycin (an mTOR inhibitor). Transcriptomic analysis HEKa revealed 12,713 differentially expressed genes (DEGs) fisetin-treated group 7,374 DEGs rapamycin-treated group, both individually treated group. Gene ontology enriched functional groups related PI3K/Akt/mTOR signaling pathways, psoriasis, development. Using silico molecular modeling, observed high binding affinity IL-17A. vitro , significantly inhibited activity, increased expression autophagy markers LC3A/B Atg5 suppressed secretion IL-17A activated lymphocytes co-cultured HEKa. Topical administration an imiquimod (IMQ)-induced mouse model exhibited better effect than reducing psoriasis-like inflammation phosphorylation promoting keratinocyte differentiation mice Fisetin also T-lymphocytes F4/80 macrophage infiltration into skin. We conclude potently inhibits pathway promotes alleviate IMQ-induced disease mice. Altogether, our findings suggest as potential treatment possibly other diseases.

Язык: Английский

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Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 4, 2024

Psoriasis is a chronic autoimmune inflammatory disease characterized by erroneous metabolism of keratinocytes. The development psoriasis closely related to abnormal activation and disorders the immune system. Dysregulated skin protective mechanisms can activate pathways within epithelial microenvironment (EIME), leading autoimmune-related diseases. In this review, we initially emphasized pathogenesis psoriasis, paying particular attention interactions between cells production cytokines in psoriasis. Subsequently, delved into significance EIME emergence A thorough understanding these processes crucial targeted therapies for Finally, discussed potential novel aimed at modulating This comprehensive examination sheds light on intricate underlying provides insights therapeutic avenues immune-mediated

Язык: Английский

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