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

Multiple roles of mitochondria in tumorigenesis and treatment: from mechanistic insights to emerging therapeutic strategies DOI Creative Commons
Min Zhang, Yuchen Yang, Jiacheng Wu

et al.

ONCOLOGIE, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

0
Immunomodulatory Effect of Nuciferine on Benzo(a)pyrene (B[a]P)-induced Lung Cancer: A Preclinical Model DOI

Fangqin Li,

Xiu-Mei Luan,

Yingying Yao

et al.

Pharmacognosy Magazine, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Background Lung cancer is a deadly type of and the primary cause cancer-related deaths in both males females worldwide. The number lung cases has risen worldwide due to growing population smokers an increase environmental pollutants. Purpose current study was dedicated studying anti-cancer immunomodulatory activities nuciferine against B[a]P-induced mice. Methods initiated BALB/c mice by challenging them with B[a]P for 4 weeks. post- pre-treatment 25 mg/kg given B[a]P-challenged mice’s body weight, tumor incidences, numbers were tabulated. biochemical markers, immunoglobulins (Igs), phase-I -II detoxification enzymes, mitochondrial enzyme assessed using standard techniques. levels inflammatory cytokines biomarkers evaluated assay kits. histopathological analysis conducted tissues experimental Results Both successfully increased weight reduced incidence, numbers. treatment effectively regulated parameters Igs. Furthermore, modulated biomarkers, cytokine levels. findings also proved efficacy cancer. Conclusion present suggest that exhibits chemopreventive properties Therefore, it evident possesses can potentially enhance chemotherapy treatments.

Language: Английский

Citations

0
Artesunate loaded core-shell nanoplatform for the chemo-chemodynamic-photothermal synergistic cancer therapy DOI

Z.H. Gan,

Chang Liu, Shaopeng Li

et al.

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: 254, P. 114810 - 114810

Published: May 17, 2025

Language: Английский

Citations

0
Mitochondria-targeting near-infrared (NIR) materials orchestrating the symphony of precision diagnosis and therapy DOI
Gao Shu, Chunrong Qu, Jun Wang

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 59, P. 102478 - 102478

Published: Sept. 9, 2024

Language: Английский

Citations

3
Mitochondria-targeted metallo-drugs against cancer: A current mechanistic perspective DOI Creative Commons

Chinmay Pal

Results in Chemistry, Journal Year: 2023, Volume and Issue: 6, P. 101149 - 101149

Published: Oct. 4, 2023

The development of novel strategies in cancer therapy continues to be a paramount research focus, with mitochondria emerging as pivotal target due their critical role cellular energetics and apoptosis regulation. Mitochondrially targeted metallo-anticancer drugs have gained prominence potential therapeutic agents, harnessing the distinct characteristics metal complexes for cytotoxicity. This review delves into complex mechanisms action that underlie these groundbreaking compounds. Dysfunction is characteristic feature cancerous cells, rendering them more susceptible disruptions energy production apoptotic pathways. complexes, through precise molecular design, offer advantage preferentially accumulating within dysfunctional organelles. extensively discusses diverse been developed, highlighting structural features rationale behind design mitochondrial targeting. Furthermore, comprehensively outlines multifaceted which induce cytotoxicity cells. These encompass reactive oxygen species (ROS), disruption membrane (ΔΨm), interference redox homeostasis, direct damage DNA mitochondria. ability modulate key signaling pathways involved regulation also elucidated. hold great promise advancing by exploiting vulnerabilities inherent cell not only sheds light on approaches but highlights mechanistic insights contribute potent cytotoxic effects.

Language: Английский

Citations

8
BAM15 as a mitochondrial uncoupler: a promising therapeutic agent for diverse diseases DOI Creative Commons

Guoji Xiong,

Kexin Zhang,

Yujie Ma

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 11, 2023

Subcellular organelles dysfunction is implicated in various diseases, including metabolic neurodegenerative cancer, and cardiovascular diseases. BAM15, a selective mitochondrial uncoupler, has emerged as promising therapeutic agent due to its ability enhance respiration flexibility. By disrupting the coupling between electron transport ATP synthesis, BAM15 dissipates proton gradient, leading increased energy expenditure. This review provides comprehensive overview of mechanism action potential applications diverse disease contexts. shown promise obesity by increasing expenditure reducing fat accumulation. In diabetes, it improves glycemic control reverses insulin resistance. Additionally, non-alcoholic fatty liver disease, sepsis, diseases mitigating oxidative stress, modulating inflammatory responses, promoting cardioprotection. The safety profile encouraging, with minimal adverse effects remarkable tolerability. However, challenges such high lipophilicity need for alternative delivery methods be addressed. Further research necessary fully understand optimize application clinical settings.

Language: Английский

Citations

8
Cancer nanomedicine: emergence, expansion, and expectations DOI Creative Commons

Keerthana Suresh Kizhakkanoodan,

Yuvraj Rallapalli,

Praveena Joyceline

et al.

SN Applied Sciences, Journal Year: 2023, Volume and Issue: 5(12)

Published: Dec. 1, 2023

Abstract The introduction of cancer nanomedicine has substantially enhanced the effectiveness treatments. Nano-formulations are becoming more prevalent among other treatment methods due to their improved therapeutic efficacy and low systemic toxicity. discovery permeability retention (EPR) effect led development numerous nanodrugs that passively target tumours. Then researchers identified certain cells overexpress receptors, targeting these over-expressing receptors using moiety on surface nanoparticles becomes promising functionalization become an important area nanomedicine. This leads physiochemical modification for strengthening EPR active targeting. review comprehensively outlines origins nanomedicine, role effect, tools nanotechnology specifications, nature passive targeting, which gives direction progress therapy briefly enlists available nano formulations different cancers attempts were made account barriers clinical translation. also describes transition research from nano-immunotherapy.

Language: Английский

Citations

6
Iridium(iii) complexes conjugated with naproxen exhibit potent anti-tumor activities by inducing mitochondrial damage, modulating inflammation, and enhancing immunity DOI

Kai Xie,

Xing-Yun Lu,

Zhu Hou

et al.

Dalton Transactions, Journal Year: 2024, Volume and Issue: 53(20), P. 8772 - 8780

Published: Jan. 1, 2024

A series of Ir(III)-naproxen (NPX) conjugates with the molecular formula [Ir(C^N)

Language: Английский

Citations

2
Mitochondrial dysfunction significantly contributes to the sensitivity of tumor cells to anoikis and their metastatic potential DOI Creative Commons
G. I. Solyanik, Denis Kolesnik, И. В. Прохорова

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(12), P. e32626 - e32626

Published: June 1, 2024

It is well-known that the survival of metastatic cells during their dissemination plays an important role in metastasis. However, does this mean final result cascade (the volume damage to distant organs and tissues) depends on, or at least correlates with, degree resistance anoikis (distinctive hallmarks cells)? This question remains open.The aim work was study vitro changes rates, proliferative activity, oxidative stress, glycolysis intensity three days anchorage-dependent anchorage-independent growth two Lewis lung carcinoma cell lines (LLC LLC/R9) compare these with status mitochondria potential vivo.MethodsThe number metastases were estimated for each line after intramuscular inoculation C57Bl/6 mice. For study, seeded on Petri dishes pretreated poly-HEMA untreated then allowed grow 3 days. Cell viability, cycle progression, level reactive oxygen species (ROS), glucose consumption lactate production rates investigated daily both conditions. An electron microscopy intracellular structures carried out.ResultsThe showed (as far as we know first time) a correlation between (determined vivo) sensitivity (assessed vitro). The transition LLC/R9 inherently defective mitochondrial system conditions characterized by decrease survival, slowdown increase rate ROS levels manyfold lower potential, compared highly LLC normal system.

Language: Английский

Citations

2
Aging through the lens of mitochondrial DNA mutations and inheritance paradoxes DOI
Jia Chen, Hongyu Li,

Runyu Liang

et al.

Biogerontology, Journal Year: 2024, Volume and Issue: 26(1)

Published: Dec. 27, 2024

Language: Английский

Citations

2