Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells

Wigner, Paulina; Zieliński, Krzysztof; Łabieniec-Watała, Magdalena; Marczak, Agnieszka; Szwed, Marzena

doi:10.1038/s41598-021-84146-4

Cited by 20 publications

(10 citation statements)

References 39 publications

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“…Doxorubicin (DOX), one of the most used chemotherapeutic drugs, − was applied as a model drug of the drug delivery system. The absorption and emission spectra of MATPE and DOX were performed.…”

Section: Resultsmentioning

confidence: 99%

Self-Luminescent Drug Delivery Vehicle: Synthesis, Self-Assembly Behavior, Cysteine-Responsive Property, and Application in the Visualization of Drug Release

Xia,

Cheng,

Liang

et al. 2023

Langmuir

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Targeted drug delivery systems have gained great attention from the chemistry and biomedical fields in recent years due to the minimized harm to normal cells. When designing targeted drug delivery systems, the property of harmlessness to normal cells and the tracking ability of the whole process are quite crucial. These two characters can be brought into the related systems by applying a drug carrier that is self-luminescent and its drug release can be induced by the microenvironment of cancer cells. Therefore, the design and synthesis of drug delivery vehicles are significant for the fabrication of target drug delivery systems. Herein, we have synthesized a cysteine-responsive and fluorescent molecule, maleic acid-modified tetraphenylethylene derivative (MATPE), by a facile method. In addition, a drug delivery system with self-luminescence and cysteine-responsiveness based on the self-assembly of MATPE was fabricated. In this system, MATPE and cysteine both played dual roles as cysteine probe/drug carrier and emission-enhanced inducement/drug-release stimulus. The drug-release process was successfully realized in cancer cells and can be visualized, exhibiting great potential in the field of theranostics.

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Section: Resultsmentioning

confidence: 99%

Self-Luminescent Drug Delivery Vehicle: Synthesis, Self-Assembly Behavior, Cysteine-Responsive Property, and Application in the Visualization of Drug Release

Xia,

Cheng,

Liang

et al. 2023

Langmuir

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“…However, in DLD , as a mitochondrial-related gene, its roles in breast cancer are poorly understood. Prior studies have noted that mitochondrial dysfunction and dynamics are closely correlated with breast cancer progression and chemosensitivity [ 14 – 17 ]. A strong relationship between ATP synthase and resistance to HER2-targeted antibody therapies has been reported [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Genes Predicting Poor Response of Trastuzumab in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer

Dong

Dai

Sun

et al. 2022

Journal of Immunology Research

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Objective. To identify trastuzumab-resistant genes predicting drug response and poor prognosis in human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Methods. Gene expression profiles from the GEO (Gene Expression Omnibus) database were obtained and analyzed. Differentially expressed genes (DEGs) between the pathological complete response (pCR) group and non-pCR group in a trastuzumab neoadjuvant therapy cohort and DEGs between Herceptin-resistant and wild-type cell lines were detected and evaluated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed to select the functional hub genes. The hub genes’ prognostic power was validated by another trastuzumab adjuvant treatment cohort. Results. Fifty upregulated overlapping DEGs were identified by analyzing two trastuzumab resistance-related GEO databases. Functional analysis picked out ten hub genes enriched in mitochondrial function and metabolism pathways: ASCL1, CPT2, DLD, ELVOL7, GAMT, NQO1, SLC23A1, SPR, UQCRB, and UQCRQ. These hub genes could distinguish patients with trastuzumab resistance from the sensitive ones. Further survival analysis of hub genes showed that DLD overexpression was significantly associated with an unfavorable prognosis in HER2+ breast cancer patients. Conclusion. Ten novel trastuzumab resistance-related genes were discovered, of which DLD could be used for trastuzumab response prediction and prognostic prediction in HER2+ breast cancer.

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“…According to earlier studies, Tf-bound DOX triggers the TRAIL-dependent, extrinsic apoptosis pathway, which results in programmed cell death. TNF-and other cytokines are present, demonstrating a connection between the conjugate's pro-inflammatory effects and its cytotoxicity (34,35).…”

Section: Mitochondrial Effects Of Anthracyclinesmentioning

confidence: 99%

Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play

Moossavi

Lu²,

Herrmann³

et al. 2023

Front. Cardiovasc. Med.

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Anthracyclines are among the most potent chemotherapeutics; however, cardiotoxicity significantly restricts their use. Indeed, anthracycline-induced cardiotoxicity (AIC) fares among the worst types of cardiomyopathy, and may only slowly and partially respond to standard heart failure therapies including β-blockers and ACE inhibitors. No therapy specifically designed to treat anthracycline cardiomyopathy at present, and neither is it known if any such strategy could be developed. To address this gap and to elucidate the molecular basis of AIC with a therapeutic goal in mind, zebrafish has been introduced as an in vivo vertebrate model about a decade ago. Here, we first review our current understanding of the basic molecular and biochemical mechanisms of AIC, and then the contribution of zebrafish to the AIC field. We summarize the generation of embryonic zebrafish AIC models (eAIC) and their use for chemical screening and assessment of genetic modifiers, and then the generation of adult zebrafish AIC models (aAIC) and their use for discovering genetic modifiers via forward mutagenesis screening, deciphering spatial-temporal-specific mechanisms of modifier genes, and prioritizing therapeutic compounds via chemical genetic tools. Several therapeutic target genes and related therapies have emerged, including a retinoic acid (RA)-based therapy for the early phase of AIC and an autophagy-based therapy that, for the first time, is able to reverse cardiac dysfunction in the late phase of AIC. We conclude that zebrafish is becoming an important in vivo model that would accelerate both mechanistic studies and therapeutic development of AIC.

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Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells

Cited by 20 publications

References 39 publications

Self-Luminescent Drug Delivery Vehicle: Synthesis, Self-Assembly Behavior, Cysteine-Responsive Property, and Application in the Visualization of Drug Release

Self-Luminescent Drug Delivery Vehicle: Synthesis, Self-Assembly Behavior, Cysteine-Responsive Property, and Application in the Visualization of Drug Release

Identification of Genes Predicting Poor Response of Trastuzumab in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer

Molecular mechanisms of anthracycline induced cardiotoxicity: Zebrafish come into play

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