Mannich Base Derived from Lawsone Inhibits PKM2 and Induces Neoplastic Cell Death DOI Creative Commons
Lucas Rubini-Dias, Tácio Vinício Amorim Fernandes,

Michele Pereira de Souza

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2916 - 2916

Published: Dec. 21, 2024

Background/Objectives: Pyruvate kinase M2, a central regulator of cancer cell metabolism, has garnered significant attention as promising target for disrupting the metabolic adaptability tumor cells. This study explores potential Mannich base derived from lawsone (MB-6a) to interfere with PKM2 enzymatic activity both in vitro and silico. Methods: The antiproliferative MB-6a was tested using MTT assay various lines, including SCC-9, Hep-G2, HT-29, B16-F10, normal human gingival fibroblast (HGF). inhibition mediated by assessed an LDH-coupled measuring ATP production. Docking studies molecular dynamics calculations were performed Autodock 4 GROMACS, respectively, on tetrameric crystallographic structure. Results: 6a demonstrated selective cytotoxicity against all lines without affecting migration, highest selectivity index (SI) 4.63 followed B16-F10 (SI = 3.9), Hep-G2 3.4), HT-29 2.03). compound effectively inhibited glycolytic activity, leading reduction production reaction cells treated this naphthoquinone derivative. showed favorable binding ATP-bound monomers through docking (PDB ID: 4FXF; affinity scores ranging −6.94 −9.79 kcal/mol) MD simulations, revealing affinities stabilized key interactions hydrogen bonds, halogen hydrophobic contacts. Conclusions: findings suggest that exerts its glucose consequently reducing triggering energetic collapse highlights lead targeting warrants further investigation into mechanism action clinical applications.

Language: Английский

IGFBP2 Promotes Proliferation and Glycolysis of Endometrial Cancer by Regulating PKM2/HIF‐1α Axis DOI Creative Commons
Yuxi Jin, Meng Qi,

Lulu Si

et al.

Cancer Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Endometrial cancer (EC) is a worldwide gynecologic malignancies, with remarking increase of incidence and mortality rates in recent years. Growing evidence indicates that glucose metabolism reprogramming the most representative metabolic signature tumor cells exploring its modulatory function EC development will promote identifying potential therapeutic targets. IGFBP2 an insulin-like growth factor binding protein which closely associated variety diseases. However, biological role effects on remain unclear. In this study, we demonstrated was highly expressed tissues correlated poor prognosis. Overexpression promoted proliferation glycolysis cells, whereas knockdown had opposite effect. Mechanistically, directly interacted PKM2, inducing weakened PKM2 degradation, expression prevented translocation to nucleus. Additionally, upregulated under condition hypoxia regulated by transcriptional activation HIF-1α. Finally, IGFBP2/PKM2/HIF-1α axis confirmed vivo using mouse xenograft models. Taken together, current study identifies as upstream activator PKM2-driven providing promising target for EC.

Language: Английский

Citations

0
Role of Ubiquitination-driven Metabolisms in Oncogenesis and Cancer Therapy DOI
Dongqin Yang, Can Yang,

Linlin Huang

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Sanguinarine Suppresses Oral Squamous Cell Carcinoma Progression by Targeting the PKM2/TFEB Aix to Inhibit Autophagic Flux DOI

Yong-Chun Peng,

Zhijing He,

Lun-cai Yin

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 136, P. 156337 - 156337

Published: Dec. 19, 2024

Language: Английский

Citations

3
Autophagy in oral cancer: Promises and challenges (Review) DOI
Zhou Li, Yao Zhang, Jianhua Lei

et al.

International Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 54(6)

Published: Oct. 17, 2024

Autophagy captures damaged or dysfunctional proteins and organelles through the lysosomal pathway to achieve proper cellular homeostasis. possesses distinct characteristics is given recognized functions in numerous physiological pathological conditions, such as cancer. Early stage cancer development can be stopped by autophagy. After tumor cells have successfully undergone transformation progressed a late stage, autophagy-mediated system of dynamic degradation recycling will support cell growth adaptation various stress responses while preserving energy In present study, dual function that autophagy plays oral contexts stages, existing arguments for against autophagy, ways which contributes modifications, carcinogenesis, drug resistance, invasion, metastasis self-proliferation, are reviewed. Special attention paid mechanisms processes, most recent findings on application certain conventional drugs natural compounds novel agents modulate discussed. Overall, further research needed determine validity reliability promotion inhibition maximizing difficult challenge increasing suppression improve clinical outcomes.

Language: Английский

Citations

1
Synthesis and biological evaluation of ortho -phenyl phenylhydroxamic acids containing phenothiazine with improved selectivity for class IIa histone deacetylases DOI Creative Commons
Kai‐Cheng Hsu,

Yunyi Huang,

Jung-Chun Chu

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 39(1)

Published: Sept. 24, 2024

Class IIa histone deacetylases (HDACs) have been linked to tumorigenesis in various cancers. Previously, we designed phenylhydroxamic acid

Language: Английский

Citations

0
Glucose Metabolism and Glucose Transporters in Head and Neck Squamous Cell Carcinoma DOI
Yanyan Ye, Zaizai Cao

Cancer Investigation, Journal Year: 2024, Volume and Issue: 42(10), P. 827 - 844

Published: Sept. 26, 2024

Head and neck squamous cell carcinoma ranks seventh globally in malignancy prevalence, with persistent high mortality rates despite treatment advancements. Glucose, pivotal cancer metabolism via the Warburg effect, enters cells glucose transporters, notably GLUT proteins. Glycolysis, aerobic oxidation, pentose phosphate pathway significantly impact HNSCC progression. exhibits elevated expression of enzymes proteins, correlating prognosis. Heterogeneity yields varied metabolic profiles, influenced by factors like HPV status disease stage. This review highlights metabolism's role potential as therapeutic targets imaging tracers HNSCC.

Language: Английский

Citations

0
Extracellular vesicle-packaged PKM2 from endometriotic stromal cells promotes endometrial collagen I deposition by inhibiting autophagy in endometriosis DOI
Yuan Zhu, Liang Gao, J. Zhang

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: unknown, P. 111523 - 111523

Published: Nov. 1, 2024

Language: Английский

Citations

0
Mannich Base Derived from Lawsone Inhibits PKM2 and Induces Neoplastic Cell Death DOI Creative Commons
Lucas Rubini-Dias, Tácio Vinício Amorim Fernandes,

Michele Pereira de Souza

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2916 - 2916

Published: Dec. 21, 2024

Background/Objectives: Pyruvate kinase M2, a central regulator of cancer cell metabolism, has garnered significant attention as promising target for disrupting the metabolic adaptability tumor cells. This study explores potential Mannich base derived from lawsone (MB-6a) to interfere with PKM2 enzymatic activity both in vitro and silico. Methods: The antiproliferative MB-6a was tested using MTT assay various lines, including SCC-9, Hep-G2, HT-29, B16-F10, normal human gingival fibroblast (HGF). inhibition mediated by assessed an LDH-coupled measuring ATP production. Docking studies molecular dynamics calculations were performed Autodock 4 GROMACS, respectively, on tetrameric crystallographic structure. Results: 6a demonstrated selective cytotoxicity against all lines without affecting migration, highest selectivity index (SI) 4.63 followed B16-F10 (SI = 3.9), Hep-G2 3.4), HT-29 2.03). compound effectively inhibited glycolytic activity, leading reduction production reaction cells treated this naphthoquinone derivative. showed favorable binding ATP-bound monomers through docking (PDB ID: 4FXF; affinity scores ranging −6.94 −9.79 kcal/mol) MD simulations, revealing affinities stabilized key interactions hydrogen bonds, halogen hydrophobic contacts. Conclusions: findings suggest that exerts its glucose consequently reducing triggering energetic collapse highlights lead targeting warrants further investigation into mechanism action clinical applications.

Language: Английский

Citations

0