Reversing Multidrug Resistance by Inducing Mitochondrial Dysfunction for Enhanced Chemo-Photodynamic Therapy in Tumor

2021 ◽  
Vol 13 (38) ◽  
pp. 45259-45268
Author(s):  
Chao Shi ◽  
Haiqiao Huang ◽  
Xiao Zhou ◽  
Zhen Zhang ◽  
He Ma ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Multidrug Resistance ◽  
Mitochondrial Dysfunction

Isomeric Ir(iii) complexes for tracking mitochondrial pH fluctuations and inducing mitochondrial dysfunction during photodynamic therapy

2019 ◽  
Vol 48 (46) ◽  
pp. 17200-17209 ◽  
Author(s):  
Haijie Chen ◽  
Chen Ge ◽  
Huiqun Cao ◽  
Xuepeng Zhang ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Mitochondrial Dysfunction ◽  
Ph Response ◽  
Ph Fluctuations

Two pairs of isomeric phosphorescent Ir(iii) complexes that show mitochondrial pH-response and induce mitochondrial dysfunction during photodynamic therapy.

Overcoming the diverse mechanisms of multidrug resistance in lung cancer cells by photodynamic therapy using pTHPP-loaded PLGA-lipid hybrid nanoparticles

2020 ◽  
Vol 149 ◽  
pp. 218-228 ◽  
Author(s):  
Sasivimon Pramual ◽  
Kriengsak Lirdprapamongkol ◽  
Valérie Jouan-Hureaux ◽  
Muriel Barberi-Heyob ◽  
Céline Frochot ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Photodynamic Therapy ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Hybrid Nanoparticles

scholarly journals Evolutionary dynamics of cancer multidrug resistance in response to olaparib and photodynamic therapy

2021 ◽  
Vol 14 (11) ◽  
pp. 101198
Author(s):  
Yan Baglo ◽  
Aaron J. Sorrin ◽  
Xiaocong Pu ◽  
Cindy Liu ◽  
Jocelyn Reader ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Multidrug Resistance ◽  
Evolutionary Dynamics

scholarly journals Mitochondrial dysfunctions trigger the calcium signaling-dependent fungal multidrug resistance

2019 ◽  
Vol 117 (3) ◽  
pp. 1711-1721 ◽  
Author(s):  
Yeqi Li ◽  
Yuanwei Zhang ◽  
Chi Zhang ◽  
Hongchen Wang ◽  
Xiaolei Wei ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Mitochondrial Dysfunction ◽  
Calcium Signaling ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Drug Binding ◽  
Fitness Cost ◽  
Drug Resistant ◽  
Resistant Mutants

Drug resistance in fungal pathogens has risen steadily over the past decades due to long-term azole therapy or triazole usage in agriculture. Modification of the drug target protein to prevent drug binding is a major recognized route to induce drug resistance. However, mechanisms for nondrug target-induced resistance remain only loosely defined. Here, we explore the molecular mechanisms of multidrug resistance resulted from an efficient adaptation strategy for survival in drug environments in the human pathogen Aspergillus fumigatus. We show that mutants conferring multidrug resistance are linked with mitochondrial dysfunction induced by defects in heme A biosynthesis. Comparison of the gene expression profiles between the drug-resistant mutants and the parental wild-type strain shows that multidrug-resistant transporters, chitin synthases, and calcium-signaling-related genes are significantly up-regulated, while scavenging mitochondrial reactive oxygen species (ROS)-related genes are significantly down-regulated. The up-regulated-expression genes share consensus calcium-dependent serine threonine phosphatase-dependent response elements (the binding sites of calcium-signaling transcription factor CrzA). Accordingly, drug-resistant mutants show enhanced cytosolic Ca2+ transients and persistent nuclear localization of CrzA. In comparison, calcium chelators significantly restore drug susceptibility and increase azole efficacy either in laboratory-derived or in clinic-isolated A. fumigatus strains. Thus, the mitochondrial dysfunction as a fitness cost can trigger calcium signaling and, therefore, globally up-regulate a series of embedding calcineurin-dependent–response-element genes, leading to antifungal resistance. These findings illuminate how fitness cost affects drug resistance and suggest that disruption of calcium signaling might be a promising therapeutic strategy to fight against nondrug target-induced drug resistance.

scholarly journals Polymeric mixed micelles loaded mitoxantrone for overcoming multidrug resistance in breast cancer via photodynamic therapy

2017 ◽  
Vol Volume 12 ◽  
pp. 6595-6604 ◽  
Author(s):  
Zeyong Li ◽  
Yuee Cai ◽  
Yiqiao Zhao ◽  
Hua Yu ◽  
Haiyu Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Multidrug Resistance ◽  
Mixed Micelles

scholarly journals Comment on evolutionary dynamics of cancer multidrug resistance in response to olaparib and photodynamic therapy

2022 ◽  
Vol 15 (1) ◽  
pp. 101249
Author(s):  
Ainhoa Madariaga ◽  
Lawrence Kasherman ◽  
Michelle McMullen ◽  
Luisa Bonilla
Keyword(s):  
Photodynamic Therapy ◽  
Multidrug Resistance ◽  
Evolutionary Dynamics
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