Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(6), P. 2698 - 2715
Published: March 15, 2024
Drug repurposing offers a valuable strategy for identifying new therapeutic applications existing drugs. Recently, disulfiram (DSF), drug primarily used alcohol addiction treatment, has emerged as potential treatment inflammatory diseases by inhibiting pyroptosis, form of programmed cell death. The activity DSF can be further enhanced the presence Cu
Language: Английский
Chinese Medical Journal, Journal Year: 2024, Volume and Issue: 137(12), P. 1389 - 1398
Published: Jan. 26, 2024
Abstract Cancer is a major global health issue. Effective therapeutic strategies can prolong patients' survival and reduce the costs of treatment. Drug repurposing, which identifies new uses for approved drugs, promising approach with advantages reducing research costs, shortening development time, increasing efficiency safety. Disulfiram (DSF), Food Administration (FDA)-approved drug used to treat chronic alcoholism, has great potential as an anticancer by targeting diverse human malignancies. Several studies show antitumor effects DSF, particularly combination DSF copper (DSF/Cu), on wide range cancers such glioblastoma (GBM), breast cancer, liver pancreatic melanoma. In this review, we summarize mechanisms DSF/Cu, including induction intracellular reactive oxygen species (ROS) various cell death signaling pathways, inhibition proteasome activity, well nuclear factor-kappa B (NF-κB) signaling. Furthermore, highlight ability DSF/Cu target cancer stem cells (CSCs), provides prevent tumor recurrence metastasis. Strikingly, inhibits several molecular targets associated resistance, therefore it becoming novel option increase sensitivity chemo-resistant radio-resistant patients. Studies may shed light its improved application clinical
Language: Английский
Citations
10
International Journal of Pharmaceutics X, Journal Year: 2024, Volume and Issue: 7, P. 100248 - 100248
Published: April 18, 2024
Disulfiram (DSF) is a second-line drug for the clinical treatment of alcoholism and has long been proven to be safe use in practice. In recent years, researchers have discovered cancer-killing activity DSF, which highly dependent on presence metal ions, particularly copper ions. Additionally, free DSF unstable easily degraded within few minutes blood circulation. Therefore, an ideal formulation should facilitate co-delivery ions safeguard throughout its biological journey before reaching targeted site. Extensive research proved that nanotechnology based formulations can effectively realize this goal by strategic encapsulation therapeutic agents nanoparticle. To more specific, accomplished through precise delivery, coordinated release at tumor site, thereby amplifying cytotoxic potential. Beyond traditional co-loading techniques, innovative approaches such as DSF-metal complex nanomaterials, also demonstrated promising results animal model stage. This review aims elucidate anticancer mechanism associated with reliance well provide comprehensive overview advances arena nanomedicine strategies ion context cancer therapy.
Language: Английский
Citations
10
Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14
Published: Sept. 12, 2023
Copper is an indispensable micronutrient for the development and replication of all eukaryotes, its redox properties are both harmful beneficial to cells. An imbalance in copper homeostasis thought be involved carcinogenesis. Importantly, cancer cell proliferation, angiogenesis, metastasis cannot separated from effects copper. Cuproposis a copper-dependent form death that differs other existing modalities regulatory death. The role cuproptosis pathogenesis nervous cardiovascular systems has been widely studied; however, impact on malignant tumors yet fully understood clinical perspective. Exploring signaling pathways related will undoubtedly provide new perspective anti-tumor drugs future. Here, we systematically review systemic cellular metabolic processes mechanisms cancer. In addition, discuss possibility targeting ion prolong survival patients, with emphasis most representative ionophores chelators. We suggest attention should paid potential value treatment specific cancers.
Language: Английский
Citations
22
Cancers, Journal Year: 2023, Volume and Issue: 15(2), P. 492 - 492
Published: Jan. 13, 2023
Aldehyde dehydrogenase 1A3 (ALDH1A3) is one of 19 ALDH enzymes expressed in humans, and it critical the production hormone receptor ligand retinoic acid (RA). We review role ALDH1A3 normal physiology, its identification as a cancer stem cell marker, modes action other diseases. often over-expressed promotes tumor growth, metastasis, chemoresistance by altering gene expression, signaling pathways, glycometabolism. The increased levels occur due to genetic amplification, epigenetic modifications, post-transcriptional regulation, post-translational modification. Finally, we potential targeting ALDH1A3, with both general inhibitors small molecules specifically designed inhibit activity.
Language: Английский
Citations
21
Clinical & Translational Oncology, Journal Year: 2023, Volume and Issue: 25(7), P. 1977 - 1990
Published: Feb. 13, 2023
Language: Английский
Citations
19
Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 356, P. 288 - 305
Published: March 8, 2023
Language: Английский
Citations
19
International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 657, P. 124187 - 124187
Published: May 1, 2024
Drug repositioning is a high-priority and feasible strategy in the field of oncology research, where unmet medical needs are continuously unbalanced. Disulfiram potential non-chemotherapeutic, adjuvant anticancer agent. However, clinical translation limited by drug's poor bioavailability. Therefore, molecular encapsulation disulfiram with cyclodextrins evaluated to enhance solubility stability drug. The present work describes for first time complexation randomly methylated-β-cyclodextrin. A parallel analytical vitro biological comparison inclusion complexes hydroxypropyl-β-cyclodextrin, methylated-β-cyclodextrin sulfobutylether-β-cyclodextrin conducted. significant drug enhancement about 1000-folds fast dissolution 1 min demonstrated. dissolution-permeation studies proliferation assays demonstrate solubility-dependent efficacy Throughout different cancer cell lines' characteristics unspecific antitumoral activity, inhibitory cyclodextrin encapsulated on melanoma (IC50 100 nM) glioblastoma 7000 lines differ magnitude. This pre-formulation screening experiment serves as proof concept using platform tool further delivery development areas.
Language: Английский
Citations
8
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(4), P. 189124 - 189124
Published: May 25, 2024
Apoptosis has traditionally been regarded as the desired cell death pathway activated by chemotherapeutic drugs due to its controlled and non-inflammatory nature. However, recent discoveries of alternative pathways have paved way for immune-stimulatory treatment approaches in cancer. Ferroptosis (dependent on iron) cuproptosis copper) hold promise selective cancer targeting overcoming drug resistance. Copper ionophores iron-bearing nano-drugs show potential clinical therapy single agents adjuvant treatments. Here we review up-to-date evidence involvement metal ion-dependent cytotoxicity classical (alkylating agents, topoisomerase inhibitors, antimetabolites, mitotic spindle inhibitors) their combinations with ferroptosis inducers, indicating prospects, advantages, obstacles use.
Language: Английский
Citations
8
Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 144, P. 107122 - 107122
Published: Jan. 14, 2024
Language: Английский
Citations
7
Chem, Journal Year: 2024, Volume and Issue: 10(6), P. 1821 - 1838
Published: Feb. 29, 2024
Language: Английский
Citations
6