Mitochondria-targeting natural product rhein conjugated with dichloroacetate as the dual inhibitor of glycolysis and oxidative phosphorylation to off energize cancer cells and induce ROS storm DOI Creative Commons
Zhili Zhang, Shiming Tang, Ming‐Hui Qi

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(11), P. 4909 - 4929

Published: March 31, 2025

Rationale: Metabolic reprogramming emerges as a remarkable hallmark of cancer cells and exhibits potential in the development metabolic modulators. Numerous small-molecule inhibitors mainly target reversing dominant-glycolysis pathway. However, energy adaptation that facilitates alternation phenotypes from glycolysis to oxidative phosphorylation (OXPHOS) undermines treatment efficacy. Thus, small molecular therapeutic agents, concurrently cutting off cellular metabolism OXPHOS trigger stress damage, hold promise for therapy. Methods: Herein, natural product rhein with capacity mitochondria-targeting was conjugated pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) form multifunction molecule drug Rhein-DCA conjugate. The ATP production inhibition, damage antitumor efficacy conjugate were evaluated both vitro vivo. Results: Rhein unit not only led effective accumulation mitochondria, but also promoted binding DCA PDK1, enhancing typical inhibition by via PDK-PDH axis. Unlike classical PDK inhibitors, which restrained restored OXPHOS, within further suppressed mitochondrial respiratory chain complex induced sustained opening permeability transition pore, destroying intractable OXPHOS. Importantly, component elevated reactive oxygen species (ROS) level disrupt thus ROS triggered release associated patterns. Simultaneously, weakened lactate-mediated immunosuppression reducing lactate levels tumor microenvironment. Eventually, polarization state tumor-associated macrophages could be effectively reversed following oral administration. Conclusion: This study designed dual-inhibitor circumvent adaptations simultaneously induce immunogenic cell death repolarization, thereby synergistically promoting

Language: Английский

Chemotoxic and phototoxic effects of liposomal co-delivery of green synthesized silver nanoparticles and ZnPcS4 for enhanced photodynamic therapy in MCF-7 breast cancer cells: An in vitro study DOI
Alexander Chota, Heidi Abrahamse, Blassan P. George

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 185, P. 117986 - 117986

Published: March 15, 2025

Language: Английский

Citations

0
Progress of research on glucose transporter proteins in hepatocellular carcinoma DOI
Zheng Ruan,

Yanjun Wang,

Lei Shi

et al.

World Journal of Hepatology, Journal Year: 2025, Volume and Issue: 17(3)

Published: March 25, 2025

Hepatocellular carcinoma (HCC) is a malignant tumour with high prevalence and mortality rate worldwide. Metabolic reprogramming of cancer cells may be major factor in the process this disease. Glucose transporter proteins (GLUTs) are members facilitator superfamily membrane transporters, playing pivotal role metabolic progression HCC. This review discusses advances study GLUTs HCC, including expression patterns, functions possibilities GLUTs. In levels closely associated aggressiveness, prognosis. A series inhibitors have been demonstrated efficacy inhibiting HCC cell growth glucose uptake vitro vivo models. These offer novel approach to treatment by reducing metabolism cells, thereby impeding growth, concurrently enhancing sensitivity chemotherapeutic agents. reminds us urgent need elucidate GLUTs’ roles determine most effective ways translate these findings into clinical practice.

Language: Английский

Citations

0
Inhibition of 6-phosphogluconate dehydrogenase suppresses esophageal squamous cell carcinoma growth and enhances the anti-tumor effects of metformin via the AMPK/mTOR pathway DOI Creative Commons
Wang Bei, Zixuan Wang,

Zhizhen Zhou

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 26, 2025

Metabolic reprogramming plays a pivotal role in the development and progression of tumors. Tumor cells rely on glycolysis as their primary energy production pathway effectively utilize biomolecules generated by pentose phosphate (PPP) for efficient biosynthesis. However, 6-phosphogluconate dehydrogenase (6PGD), crucial enzyme PPP, remains unexplored esophageal squamous cell carcinoma (ESCC). In this study, we observed significant upregulation 6PGD expression ESCC tissues, which correlated with an unfavorable prognosis among patients. The experiments demonstrated that knockdown induces oxidative stress suppresses proliferation. Mechanistically, is achieved through AMPK activation subsequent inhibition downstream mTOR phosphorylation. Moreover, physcion has been found to inhibit activity exert its anti-ESCC effect via AMPK/mTOR pathway. Subsequently, conducted both vitro vivo validate anticancer efficacy combining metformin, activator, physcion. results significantly enhanced growth. This study elucidates impact proliferation along underlying molecular mechanisms, highlighting potential therapeutic target ESCC. Furthermore, investigated novel approach improved anti-tumor therapy involving metformin. These findings will contribute new insights clinical treatment strategies while providing theoretical foundation developing targeted therapies.

Language: Английский

Citations

0
Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy DOI Creative Commons

Chen‐Wei Jiang,

Minglu Tang,

Yun Su

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Mitochondria-targeting natural product rhein conjugated with dichloroacetate as the dual inhibitor of glycolysis and oxidative phosphorylation to off energize cancer cells and induce ROS storm DOI Creative Commons
Zhili Zhang, Shiming Tang, Ming‐Hui Qi

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(11), P. 4909 - 4929

Published: March 31, 2025

Rationale: Metabolic reprogramming emerges as a remarkable hallmark of cancer cells and exhibits potential in the development metabolic modulators. Numerous small-molecule inhibitors mainly target reversing dominant-glycolysis pathway. However, energy adaptation that facilitates alternation phenotypes from glycolysis to oxidative phosphorylation (OXPHOS) undermines treatment efficacy. Thus, small molecular therapeutic agents, concurrently cutting off cellular metabolism OXPHOS trigger stress damage, hold promise for therapy. Methods: Herein, natural product rhein with capacity mitochondria-targeting was conjugated pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) form multifunction molecule drug Rhein-DCA conjugate. The ATP production inhibition, damage antitumor efficacy conjugate were evaluated both vitro vivo. Results: Rhein unit not only led effective accumulation mitochondria, but also promoted binding DCA PDK1, enhancing typical inhibition by via PDK-PDH axis. Unlike classical PDK inhibitors, which restrained restored OXPHOS, within further suppressed mitochondrial respiratory chain complex induced sustained opening permeability transition pore, destroying intractable OXPHOS. Importantly, component elevated reactive oxygen species (ROS) level disrupt thus ROS triggered release associated patterns. Simultaneously, weakened lactate-mediated immunosuppression reducing lactate levels tumor microenvironment. Eventually, polarization state tumor-associated macrophages could be effectively reversed following oral administration. Conclusion: This study designed dual-inhibitor circumvent adaptations simultaneously induce immunogenic cell death repolarization, thereby synergistically promoting

Language: Английский

Citations

0