Effects of PD-L1 Inhibitors on Mitochondrial Function in Melanoma A375 Cells: Unveiling a Shielded Drug Resistance Mechanism DOI Creative Commons

宁 张,

Fenglan Feng,

Ruonan Dang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 9, 2024

Abstract Background: Resistance to immune checkpoint inhibitors, particularly PD-L1 poses a significant challenge in cancer treatment by limiting patient survival. The intricate mechanisms underlying this resistance remain poorly understood, highlighting critical gap oncology research. Objective: This study aimed delve into the regulatory impacts of inhibitors on mitochondrial function within melanoma cells (A375) and explore potential correlation between function. Methods: 1. A375 were treated with effects gene expression, respiratory chain complex IV activity, reactive oxygen species (ROS) levels, apoptosis-related genes (BAX BCL-2) tumor pathogenicity-related indicators (cell viability, migration, invasion) observed. 2. Fluorescently labeled mitochondria membrane, cell nucleus, used high-resolution confocal microscopy determine whether can enter mitochondria. 3. subjected intervention inhibitor, succinate carrier observe mRNA BCL-2 expression), invasion). Results: 1.Through microscopy, it was observed that penetrated mitochondria, binding cristae inner membrane without entering nucleus.2.Treatment resulted increased expression reduced ROS elevated BAX decreased diminished migration invasion cells.3.Inhibition impeded enhancement induced cells. led sustained increase decrease notable reduction invasion. Conclusion: exhibit capability penetrate exerting an inhibitory effect activity while significantly enhancing Disrupting reverses their overall anti-tumor efficacy, hinting at novel mechanism mediated through regulation pathway inhibitors.

Language: Английский

Reactive Oxygen Species: A Crosslink between Plant and Human Eukaryotic Cell Systems DOI Open Access
Wei Guo, Yadi Xing, Xiumei Luo

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13052 - 13052

Published: Aug. 22, 2023

Reactive oxygen species (ROS) are important regulating factors that play a dual role in plant and human cells. As the first messenger response organisms, ROS coordinate signals growth, development, metabolic activity pathways. They also can act as an alarm mechanism, triggering cellular responses to harmful stimuli. However, excess cause oxidative stress-related damage oxidize organic substances, leading malfunctions. This review summarizes current research status mechanisms of eukaryotic cells, highlighting differences similarities between two elucidating their interactions with other reactive substances ROS. Based on similar regulatory pathways kingdoms, this proposes future developments provide opportunities develop novel strategies for treating diseases or creating greater agricultural value.

Language: Английский

Citations

36
The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways DOI Creative Commons
Maryam Bakhtiyari, Mahsa Liaghat,

Fatemeh Aziziyan

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 21, 2023

Abstract Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation cells in bone marrow microenvironment (BMM). The BMM plays pivotal role promoting AML progression, angiogenesis, metastasis. immune checkpoints (ICs) metabolic processes are key players this process. In review, we delineate checkpoint characteristics BMM, with focus on roles e.g. tumor-associated macrophages, natural killer cells, dendritic profiles related signaling pathways. We also discuss pathways stimulated factors that lead to progression. then delve into metastasis, cell proliferation, including co-stimulatory inhibitory ICs. Lastly, potential therapeutic approaches future directions for treatment, emphasizing targeting as prognostic targets. conclusion, modulation these through use directed drugs opens up new promising avenues combating AML. Thereby, comprehensive elucidation significance cells' leukemic can be undertaken investigations. Additionally, should considered plausible multi-targeted therapies combination other conventional treatments

Language: Английский

Citations

31
Complex II ambiguities—FADH2 in the electron transfer system DOI Creative Commons
Erich Gnaiger

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 300(1), P. 105470 - 105470

Published: Nov. 22, 2023

The prevailing notion that reduced cofactors NADH and FADH

Language: Английский

Citations

23
Mitochondrial signaling pathways and their role in cancer drug resistance DOI
Ashwani Sharma, Tarun Virmani, Girish Kumar

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 122, P. 111329 - 111329

Published: Aug. 5, 2024

Language: Английский

Citations

9
Modification in Structures of Active Compounds in Anticancer Mitochondria-Targeted Therapy DOI Open Access
Agnieszka Felczykowska, Anna Herman-Antosiewicz

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1376 - 1376

Published: Feb. 6, 2025

Cancer is a multifaceted disease characterised by uncontrolled cellular proliferation and metastasis, resulting in significant global mortality. Current therapeutic strategies, including surgery, chemotherapy, radiation therapy, face challenges such as systemic toxicity tumour resistance. Recent advancements have shifted towards targeted therapies that act selectively on molecular structures within cancer cells, reducing off-target effects. Mitochondria emerged pivotal targets this approach, given their roles metabolic reprogramming, retrograde signalling, oxidative stress, all of which drive the malignant phenotype. Targeting mitochondria offers promising strategy to address these mechanisms at origin. Synthetic derivatives natural compounds hold particular promise mitochondrial-targeted therapies. Innovations drug design, use conjugates nanotechnology, focus optimizing for mitochondrial specificity. Such enhance efficacy while minimizing toxicity, presenting step forward modern anticancer strategies.

Language: Английский

Citations

1
Mitochondrial inhibitors: a new horizon in breast cancer therapy DOI Creative Commons

Yalan Yan,

Sijie Li,

Lanqian Su

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Breast cancer, due to resistance standard therapies such as endocrine therapy, anti-HER2 therapy and chemotherapy, continues pose a major health challenge. A growing body of research emphasizes the heterogeneity plasticity metabolism in breast cancer. Because differences subtypes exhibit bias toward metabolic pathways, targeting mitochondrial inhibitors shows great potential stand-alone or adjuvant cancer therapies. Multiple therapeutic candidates are currently various stages preclinical studies clinical openings. However, specific have been shown face multiple challenges (e.g., single therapies, structure enzymes, etc.), combining with pathways may be necessary. In this paper, we review critical role functions, including oxidative phosphorylation (OXPHOS), tricarboxylic acid cycle, fatty amino metabolism, reprogramming cells. addition, outline impact dysfunction on different aiming provide additional ideas for development improve efficacy existing

Language: Английский

Citations

6
Rosmarinic Acid-Rich Perilla frutescens Extract-Derived Silver Nanoparticles: A Green Synthesis Approach for Multifunctional Biomedical Applications including Antibacterial, Antioxidant, and Anticancer Activities DOI Creative Commons

Vasudeva Reddy Netala,

Tianyu Hou, Siva Sankar Sana

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(6), P. 1250 - 1250

Published: March 12, 2024

This study describes a simple, cost-effective, and eco-friendly method for synthesizing silver nanoparticles using rosmarinic acid extract from Perilla frutescens (PFRAE) as the bioreduction agent. The resulting nanoparticles, called PFRAE-AgNPs, were characterized various analytical techniques. UV–Vis spectrum confirmed formation of FTIR indicated participation in their synthesis stabilization. XRD pattern revealed crystal structure TEM analysis showed spherical morphology with sizes ranging between 20 80 nm. DLS that PFRAE-AgNPs monodispersed an average diameter 44.0 ± 3.2 nm, high negative zeta potential (−19.65 mV) stability. In antibacterial assays, potent activity against both Gram-positive (Bacillus subtilis Staphylococcus aureus) Gram-negative (Escherichia coli Pseudomonas aeruginosa) bacterial pathogens, suggesting they could be used agent clinical setting. Moreover, antioxidant DPPH ABTS radical scavengers highlights treatment oxidative stress-related diseases. also demonstrated significant anticancer range cell lines including human colon cancer (COLO205), prostate carcinoma (PC-3), lung adenocarcinoma (A549), ovarian (SKOV3) therapy. may have drug delivery, small size stability enable them to cross biological barriers deliver drugs specific target sites. addition aforementioned properties, found biocompatible towards normal (CHO) cells, which is crucial characteristic application therapy delivery systems. Their antibacterial, antioxidant, properties make promising candidates development new therapeutic agents. Furthermore, size, stability, biocompatibility systems enhance efficacy reduce side effects.

Language: Английский

Citations

5
New insights on mitochondrial heteroplasmy observed in ovarian diseases DOI Creative Commons
Yong Zhou, Yang Jin, Tianyu Wu

et al.

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 65, P. 211 - 226

Published: Dec. 6, 2023

The reportedly high mutation rate of mitochondrial DNA (mtDNA) may be attributed to the absence histone protection and complete repair mechanisms. Mitochondrial heteroplasmy refers coexistence wild-type mutant mtDNA. Most healthy individuals carry a low point load (<1%) in their mtDNA, typically without any discernible phenotypic effects. However, as it exceeds certain threshold, cause onset various diseases. Since ovary is highly energy-intensive organ, relies heavily on function. can potentially contribute variety significant ovarian disorders. Review: In this review, we have elucidated close relationship between mtDNA diseases, summarized novel avenues strategies for potential treatment these Key Scientific Concepts disorders, including polycystic syndrome, premature insufficiency, endometriosis. Current related are untargeted bioavailability. Nanoparticle delivery systems loaded with modulators, replacement/transplantation therapy, mitochondria-targeted gene editing therapy offer promising paths towards more effective treatments despite ongoing challenges.

Language: Английский

Citations

11
Death-associated protein 3 in cell death and beyond DOI
Ting Cao, Xuling Luo,

Zheng Binjiao

et al.

Genome Instability & Disease, Journal Year: 2024, Volume and Issue: 5(2), P. 51 - 60

Published: March 4, 2024

Language: Английский

Citations

4
Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox Homeostasis DOI Creative Commons
Raffaella Chiaramonte,

Giulia Sauro,

Domenica Giannandrea

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 115 - 115

Published: Jan. 20, 2025

The role of mitochondria as the electric engine cells is well established. Over past two decades, accumulating evidence has pointed out that, despite presence a highly active glycolytic pathway (Warburg effect), functional and even upregulated mitochondrial respiration occurs in cancer to meet need high energy biosynthetic demand sustain their anabolic growth. Mitochondria are also primary source intracellular ROS. Cancer maintain moderate levels ROS promote tumorigenesis, metastasis, drug resistance; indeed, once cytotoxicity threshold exceeded, trigger oxidative damage, ultimately leading cell death. Based on this, metabolic functions generation considered attractive targets synthetic natural anticancer compounds. Tocotrienols (TTs), specifically δ- γ-TT isoforms, vitamin E-derived biomolecules widely shown possess striking properties since they regulate several molecular pathways. Herein, we provide for first time an overview reprogramming redox homeostasis perturbation occurring cells, highlighting involvement TTs. This sheds light use these compounds promising preventive or therapeutic approach novel strategies.

Language: Английский

Citations

0