Cancer drug resistance: rationale for drug delivery systems and targeted inhibition of HSP90 family proteins

Mathieu, Cécile; Messaoudi, Samir; Fattal, Elias; Vergnaud-Gauduchon, Juliette

doi:10.20517/cdr.2019.26

Cited by 5 publications

(3 citation statements)

References 128 publications

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“…Cancer research has demonstrated that Hsp90 promotes malignant behaviors of cancer cells (Lacey and Lacey, 2021 ), such as uncontrolled proliferation, immune evasion, therapy resistance, and so on. Disruption of the chaperone mechanism of Hsp90 represents a potential method to inhibit tumor, as it can enhance the drug sensitivity of cancer cells (Li et al, 2019 ; Mathieu et al, 2019 ). Studies in fungi have demonstrated that elevated Hsp90 levels expedite the emergence of resistance to fungicides (Iyer et al, 2022 ), while reducing Hsp90 activity significantly increases the efficacy of fungicides (Fu et al, 2022 ; Li et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome reveals the role of the htpG gene in mediating antibiotic resistance through cell envelope modulation in Vibrio mimicus SCCF01

Qin,

Peng,

Feng

et al. 2024

Front. Microbiol.

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HtpG, a bacterial homolog of the eukaryotic 90 kDa heat-shock protein (Hsp90), represents the simplest member of the heat shock protein family. While the significance of Hsp90 in fungal and cancer drug resistance has been confirmed, the role of HtpG in bacterial antibiotic resistance remains largely unexplored. This research aims to investigate the impact of the htpG gene on antibiotic resistance in Vibrio mimicus. Through the creation of htpG gene deletion and complementation strains, we have uncovered the essential role of htpG in regulating the structural integrity of the bacterial cell envelope. Our transcriptomics analysis demonstrates that the deletion of htpG increases the sensitivity of V. mimicus to antimicrobial peptides, primarily due to upregulated lipopolysaccharide synthesis, reduced glycerophospholipid content, and weakened efflux pumps activity. Conversely, reduced sensitivity to β-lactam antibiotics in the ΔhtpG strain results from decreased peptidoglycan synthesis and dysregulated peptidoglycan recycling and regulation. Further exploration of specific pathway components is essential for a comprehensive understanding of htpG-mediated resistance mechanisms, aiding in the development of antimicrobial agents. To our knowledge, this is the first effort to explore the relationship between htpG and drug resistance in bacteria.

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Section: Introductionmentioning

confidence: 99%

Transcriptome reveals the role of the htpG gene in mediating antibiotic resistance through cell envelope modulation in Vibrio mimicus SCCF01

Qin,

Peng,

Feng

et al. 2024

Front. Microbiol.

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“…The therapeutic efficacy of PTT is directly influenced by intracellular HSP expression levels, which have both protective and detrimental effects on cancer cells. Thus, the efficacy of hyperthermia therapy can be increased by inhibiting HSPs, which can reduce the thermal resistance of cancer cells and potentiate the cell-killing effect of hyperthermia [228]. Currently, HSP inhibitors are being used in combination with hyperthermia.…”

Section: Photothermal and Modulated Electro-hyperthermia Therapymentioning

confidence: 99%

The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics

Somu,

Mohanty,

Basavegowda

et al. 2024

Cancers

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Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e.g., HSP10 and HSP27), HSP40, HSP60, HSP70, HSP90, and the category of large HSPs that include HSP100 and ClpB proteins. The overexpression of HSPs is induced to counteract cell stress at elevated levels in a variety of solid tumors, including anticancer chemotherapy, and is closely related to a worse prognosis and therapeutic resistance to cancer cells. HSPs are also involved in anti-apoptotic properties and are associated with processes of cancer progression and development, such as metastasis, invasion, and cell proliferation. This review outlines the previously mentioned HSPs and their significant involvement in diverse mechanisms of tumor advancement and metastasis, as well as their contribution to identifying potential targets for therapeutic interventions.

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“…To determine the susceptibility of RI and RII strains to QoIs, four fungicides were selected: trifloxystrobin (Tri), kresoxim-methyl (Kre), azoxystrobin (Azo), and pyraclostrobin (Pyr), which target the Qo site of the cytochrome bc1 complex. Additionally, seven other fungicides were selected to determine susceptibility: cyazofamid (Cya, targeted to the Qi site of the cytochrome bc1 complex), penthiopyrad (Pen, which targets the ubiquinone binding site), terbinafine (Ter, which inhibits lanosterol 14α-demethylase), fludioxonil (Flu, which is involved in the high-osmolarity glycerol (HOG) stress response signal transduction pathway), tolnaftate (Tol, which inhibits ergosterol production), difenoconazole (Dif, which inhibits fungal lanosterol-14α-demethylase activity and blocks ergosterol biosynthesis), and carbendazim (Car, which hinders microtubule assembly and disrupts spindle formation) [50][51][52][53][54][55]. Among them, Car was dissolved with 0.2 M HCL and the other fungicides were dissolved with DMSO.…”

Section: Sensitivity Test To Fungicidesmentioning

confidence: 99%

Transcriptome Analysis Reveals the Involvement of Mitophagy and Peroxisome in the Resistance to QoIs in Corynespora cassiicola

Sun,

Zhou,

Zhu

et al. 2023

Microorganisms

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Quinone outside inhibitor fungicides (QoIs) are crucial fungicides for controlling plant diseases, but resistance, mainly caused by G143A, has been widely reported with the high and widespread use of QoIs. However, two phenotypes of Corynespora casiicola (RI and RII) with the same G143A showed significantly different resistance to QoIs in our previous study, which did not match the reported mechanisms. Therefore, transcriptome analysis of RI and RII strains after trifloxystrobin treatment was used to explore the new resistance mechanism in this study. The results show that 332 differentially expressed genes (DEGs) were significantly up-regulated and 448 DEGs were significantly down-regulated. The results of GO and KEGG enrichment showed that DEGs were most enriched in ribosomes, while also having enrichment in peroxide, endocytosis, the lysosome, autophagy, and mitophagy. In particular, mitophagy and peroxisome have been reported in medicine as the main mechanisms of reactive oxygen species (ROS) scavenging, while the lysosome and endocytosis are an important organelle and physiological process, respectively, that assist mitophagy. The oxidative stress experiments showed that the oxidative stress resistance of the RII strains was significantly higher than that of the RI strains: specifically, it was more than 1.8-fold higher at a concentration of 0.12% H2O2. This indicates that there is indeed a significant difference in the scavenging capacity of ROS between the two phenotypic strains. Therefore, we suggest that QoIs’ action caused a high production of ROS, and that scavenging mechanisms such as mitophagy and peroxisomes functioned in RII strains to prevent oxidative stress, whereas RI strains were less capable of resisting oxidative stress, resulting in different resistance to QoIs. In this study, it was first revealed that mitophagy and peroxisome mechanisms available for ROS scavenging are involved in the resistance of pathogens to fungicides.

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Cancer drug resistance: rationale for drug delivery systems and targeted inhibition of HSP90 family proteins

Cited by 5 publications

References 128 publications

Transcriptome reveals the role of the htpG gene in mediating antibiotic resistance through cell envelope modulation in Vibrio mimicus SCCF01

Transcriptome reveals the role of the htpG gene in mediating antibiotic resistance through cell envelope modulation in Vibrio mimicus SCCF01

The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics

Transcriptome Analysis Reveals the Involvement of Mitophagy and Peroxisome in the Resistance to QoIs in Corynespora cassiicola

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