| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Buchtova, T, et al.
(författare)
-
Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics
- 2023
-
Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:3
-
Tidskriftsartikel (refereegranskat)abstract
- Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is gaining popularity as a supportive therapy during cancer treatment, often in combination with standard-of-care cancer chemotherapeutics. However, CBD is a biologically active substance that modulates various cellular targets, thereby possibly resulting in unpredictable outcomes, especially in combinations with other medications and therapeutic modalities. In this review, we summarize the current knowledge of CBD interactions with selected anticancer chemotherapeutics, discuss the emerging mechanistic basis for the observed biological effects, and highlight both the potential benefits and risks of such combined treatments. Apart from the experimental and preclinical results, we also indicate the planned or ongoing clinical trials aiming to evaluate the impact of CBD combinations in oncology. The results of these and future trials are essential to provide better guidance for oncologists to judge the benefit-versus-risk ratio of these exciting treatment strategies. We hope that our present overview of this rapidly advancing field of biomedicine will inspire more preclinical and clinical studies to further our understanding of the underlying biology and optimize the benefits for cancer patients.
|
|
| 5. |
- Chroma, K, et al.
(författare)
-
A drug repurposing strategy for overcoming human multiple myeloma resistance to standard-of-care treatment
- 2022
-
Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 13:3, s. 203-
-
Tidskriftsartikel (refereegranskat)abstract
- Despite several approved therapeutic modalities, multiple myeloma (MM) remains an incurable blood malignancy and only a small fraction of patients achieves prolonged disease control. The common anti-MM treatment targets proteasome with specific inhibitors (PI). The resulting interference with protein degradation is particularly toxic to MM cells as they typically accumulate large amounts of toxic proteins. However, MM cells often acquire resistance to PIs through aberrant expression or mutations of proteasome subunits such as PSMB5, resulting in disease recurrence and further treatment failure. Here we propose CuET—a proteasome-like inhibitor agent that is spontaneously formed in-vivo and in-vitro from the approved alcohol-abuse drug disulfiram (DSF), as a readily available treatment effective against diverse resistant forms of MM. We show that CuET efficiently kills also resistant MM cells adapted to proliferate under exposure to common anti-myeloma drugs such as bortezomib and carfilzomib used as the first-line therapy, as well as to other experimental drugs targeting protein degradation upstream of the proteasome. Furthermore, CuET can overcome also the adaptation mechanism based on reduced proteasome load, another clinically relevant form of treatment resistance. Data obtained from experimental treatment-resistant cellular models of human MM are further corroborated using rather unique advanced cytotoxicity experiments on myeloma and normal blood cells obtained from fresh patient biopsies including newly diagnosed as well as relapsed and treatment-resistant MM. Overall our findings suggest that disulfiram repurposing particularly if combined with copper supplementation may offer a promising and readily available treatment option for patients suffering from relapsed and/or therapy-resistant multiple myeloma.
|
|
| 6. |
- Mistrik, M, et al.
(författare)
-
Microthermal-induced subcellular-targeted protein damage in cells on plasmonic nanosilver-modified surfaces evokes a two-phase HSP-p97/VCP response
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 713-
-
Tidskriftsartikel (refereegranskat)abstract
- Despite proteotoxic stress and heat shock being implicated in diverse pathologies, currently no methodology to inflict defined, subcellular thermal damage exists. Here, we present such a single-cell method compatible with laser-scanning microscopes, adopting the plasmon resonance principle. Dose-defined heat causes protein damage in subcellular compartments, rapid heat-shock chaperone recruitment, and ensuing engagement of the ubiquitin–proteasome system, providing unprecedented insights into the spatiotemporal response to thermal damage relevant for degenerative diseases, with broad applicability in biomedicine. Using this versatile method, we discover that HSP70 chaperone and its interactors are recruited to sites of thermally damaged proteins within seconds, and we report here mechanistically important determinants of such HSP70 recruitment. Finally, we demonstrate a so-far unsuspected involvement of p97(VCP) translocase in the processing of heat-damaged proteins. Overall, we report an approach to inflict targeted thermal protein damage and its application to elucidate cellular stress-response pathways that are emerging as promising therapeutic targets.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
