In Silico Discovery of a Novel Natural Product Targeting PI3Kα for the Treatment of Head and Neck Squamous Cell Carcinoma

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3565 - 3565

Published: April 10, 2025

Head and neck squamous cell carcinoma (HNSCC) remains a major health burden, with abnormal activation of phosphatidylinositol 3-kinase alpha (PI3Kα) strongly implicated in its pathogenesis. Targeting PI3Kα represents promising therapeutic strategy. In this study, we employed structure-based virtual screening to identify natural small-molecule inhibitors PI3Kα. A total 12,800 molecules were screened, five compounds selected for further evaluation based on binding affinity interaction patterns. Pharmacokinetic properties assessed using ADMET predictions, molecular dynamics (MD) simulations conducted validate the stability. Among candidates, Apigetrin demonstrated favorable properties, high safety profile, stable within ATP-binding pocket These findings suggest that is inhibitor potential relevance HNSCC.

Language: Английский

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CKS1B regulates the radiosensitivity of lung cancer via activating the PI3K/AKT signaling pathway

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111828 - 111828

Published: April 1, 2025

Language: Английский

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Ferroptosis and oral squamous cell carcinoma: connecting the dots to move forward

Frontiers in Oral Health, Journal Year: 2024, Volume and Issue: 5

Published: Sept. 4, 2024

Oral squamous cell carcinoma (OSCC) is an aggressive disease whose incomplete biological comprehension contributes to the inappropriate clinical management and poor prognosis. Thus, identification of new promising molecular targets treat OSCC paramount importance. Ferroptosis a regulated death caused by iron-dependent accumulation reactive oxygen species consequent oxidative damage lipid membranes. Over last five years, growing number studies has reported that sensitive ferroptosis induction inducers exert remarkable antitumor effect in OSCC, even those displaying low response common approaches, such as chemotherapy radiotherapy. In addition, considered immunogenic death, it may modulate immune against OSCC. this review, we summarize so far identified regulatory mechanisms prognostic models based on ferroptosis-related genes discuss perspective inducing novel strategy directly or, alternatively, improve sensitivity other approaches. Finally, integrate data emerging from research studies, reviewed here, through silico analysis provide personal potential interconnection between autophagy

Language: Английский

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Engineering PD-L1 targeted liposomal canagliflozin achieves multimodal synergistic cancer therapy

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 498, P. 155074 - 155074

Published: Aug. 23, 2024

Language: Английский

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MiR‐4524b‐5p‐targeting ALDH1A3 attenuates the proliferation and radioresistance of glioblastoma via PI3K/AKT/mTOR signaling

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 30(2)

Published: Aug. 8, 2023

Abstract Increasing evidence has revealed a strong connection between the aldehyde dehydrogenase family member ALDH1A3 and tumorigenesis, therapy resistance, prognosis in diverse types of cancer. However, specific miRNA involved pathways that regulate ALDH1A3‐mediated glioblastoma (GBM) radioresistance remains to be elucidated. In this study, we demonstrated high expression GBM cells, which plays critical role their proliferation radioresistance. We also identified miR‐4524b‐5p, is downregulated GBM, as upstream regulator. Overexpression miR‐4524b‐5p reduced cells. Moreover, silencing PI3K/AKT/mTOR signaling glycolytic activity whereas inhibiting mTOR reversed effects on these vivo experiments have evidenced overexpression significantly tumor growth cells summary, targeting axis promising therapeutic strategy for treating GBM.

Language: Английский

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MiR-630 Promotes Radioresistance by Induction of Anti-Apoptotic Effect via Nrf2–GPX2 Molecular Axis in Head–Neck Cancer

Cells, Journal Year: 2023, Volume and Issue: 12(24), P. 2853 - 2853

Published: Dec. 17, 2023

Head and neck cancer (HNC) ranks among the top ten prevalent cancers worldwide. Radiotherapy stands as a pivotal treatment component for HNC; however, radioresistance in cancerous cells often leads to local recurrence, becoming substantial factor failure. MicroRNAs (miRNAs) are compact, non-coding RNAs that regulate gene expression by targeting mRNAs inhibit protein translation. Although several studies have indicated dysregulation of miRNAs is intricately linked with malignant transformation, understanding this molecular family’s role remains limited. This study determined miR-630 regulating radiosensitivity HNC. We discovered functions an oncomiR, marked its overexpression HNC patients, correlating poorer prognosis. further delineated function cells. While it had minimal impact on cell growth, contributed result was supported decreased cellular apoptosis caspase enzyme activities. Moreover, mitigated irradiation-induced DNA damage, evidenced reduced levels γ-H2AX histone protein, marker double-strand breaks. Mechanistically, ROS initiated Nrf2 transcriptional activity, resulting upregulation antioxidant GPX2. Thus, elucidates augments inducing anti-apoptotic effect via Nrf2–GPX2 axis The modulation may serve novel radiosensitizing target

Language: Английский

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Public neoantigens in breast cancer immunotherapy (Review)

International Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 54(1)

Published: June 17, 2024

Among women globally, breast cancer is the most prevalent and leading cause of cancer‑related death. Interestingly, though genetic mutations contribute to disease, <15% diagnosed with have a family history suggesting prevalence sporadic in development. In rapidly rising field genomics, neoantigen‑based immunotherapy has come fore. The investigation novel proteins arising from unique somatic or neoantigens opened new pathway for both individualized public treatments. Because they are shared among individuals similar changes, provide an opportunity 'off‑the‑shelf' anticancer therapies, potentially extending benefits wider patient group. present review aimed highlight role as therapeutic targets patients cancer, emphasizing common hotspot certain genes identified cancer. clinical utilization therapies treatment were also discussed.

Language: Английский

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The Role of the PI3K/Akt/mTOR Axis in Head and Neck Squamous Cell Carcinoma

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1610 - 1610

Published: July 19, 2024

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies globally, representing a significant public health problem with poor prognosis. The development efficient therapeutic strategies for HNSCC prevention treatment urgently needed. PI3K/AKT/mTOR (PAM) signaling pathway highly conserved transduction network in eukaryotic cells that promotes survival, growth, cycle progression. Dysfunction components this pathway, such as hyperactivity PI3K, loss PTEN function, gain-of-function mutations AKT, are well-known drivers resistance disease progression cancer. In review, we discuss major dysregulations PAM HNSCC. We highlight results clinical trials involving inhibitors targeting strategy treating Additionally, examine primary mechanisms to drugs potential strategies.

Language: Английский

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Unveiling the nexus: Long non-coding RNAs and the PI3K/Akt pathway in oral squamous cell carcinoma

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 262, P. 155540 - 155540

Published: Aug. 12, 2024

Language: Английский

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CTSG restraines the proliferation and metastasis of head and neck squamous cell carcinoma by blocking the JAK2/STAT3 pathway

Cellular Signalling, Journal Year: 2024, Volume and Issue: 127, P. 111562 - 111562

Published: Dec. 11, 2024

Language: Английский

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