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- Sazonova, EV, et al.
(författare)
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A link between mitotic defects and mitotic catastrophe: detection and cell fate
- 2021
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Ingår i: Biology direct. - : Springer Science and Business Media LLC. - 1745-6150. ; 16:1, s. 25-
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Tidskriftsartikel (refereegranskat)abstract
- Although the phenomenon of mitotic catastrophe was first described more than 80 years ago, only recently has this term been used to explain a mechanism of cell death linked to delayed mitosis. Several mechanisms have been suggested for mitotic catastrophe development and cell fate. Depending on molecular perturbations, mitotic catastrophe can end in three types of cell death, namely apoptosis, necrosis, or autophagy. Moreover, mitotic catastrophe can be associated with different types of cell aging, the development of which negatively affects tumor elimination and, consequently, reduces the therapeutic effect. The effective triggering of mitotic catastrophe in clinical practice requires induction of DNA damage as well as inhibition of the molecular pathways that regulate cell cycle arrest and DNA repair. Here we discuss various methods to detect mitotic catastrophe, the mechanisms of its development, and the attempts to use this phenomenon in cancer treatment.
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| 2. |
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| 3. |
- Sazonova, EV, et al.
(författare)
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Drug toxicity assessment: cell proliferation versus cell death
- 2022
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Ingår i: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 8:1, s. 417-
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of the toxicity of chemotherapeutic drugs is one of the main tasks of clinical pharmacology. Decreased viability of tumor cells may reflect two important physiological processes, namely the arrest of proliferation associated with disturbances in cellular metabolism or actual cell death. Elucidation of the exact processes mediating a reduction in the number of cells is fundamentally important to establish the mechanisms of drug action. Only the use of a combination of cell biological and biochemical approaches makes it possible to understand these mechanisms. Here, using various lines of tumor cells and a set of methodological approaches, we carried out a detailed comparative analysis and demonstrated the possible ways to overcome the uncertainties in establishing the mechanisms of cell response to the action of chemotherapeutic drugs and their toxicity.
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| 4. |
- Sazonova, EV, et al.
(författare)
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Platinum drugs and taxanes: can we overcome resistance?
- 2021
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Ingår i: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 7:1, s. 155-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer therapy is aimed at the elimination of tumor cells and acts via the cessation of cell proliferation and induction of cell death. Many research publications discussing the mechanisms of anticancer drugs use the terms “cell death” and “apoptosis” interchangeably, given that apoptotic pathways are the most common components of the action of targeted and cytotoxic compounds. However, there is sound evidence suggesting that other mechanisms of drug-induced cell death, such as necroptosis, ferroptosis, autophagy, etc. may significantly contribute to the fate of cancer cells. Molecular cross-talks between apoptotic and nonapoptotic death pathways underlie the successes and the failures of therapeutic interventions. Here we discuss the nuances of the antitumor action of two groups of the widely used anticancer drugs, i.e., platinum salts and taxane derivatives. The available data suggest that intelligent interference with the choice of cell death pathways may open novel opportunities for cancer treatment.
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| 5. |
- Senichkin, VV, et al.
(författare)
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Bak and Bcl-xL Participate in Regulating Sensitivity of Solid Tumor Derived Cell Lines to Mcl-1 Inhibitors
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- BH3 mimetics represent a promising tool in cancer treatment. Recently, the drugs targeting the Mcl-1 protein progressed into clinical trials, and numerous studies are focused on the investigation of their activity in various preclinical models. We investigated two BH3 mimetics to Mcl-1, A1210477 and S63845, and found their different efficacies in on-target doses, despite the fact that both agents interacted with the target. Thus, S63845 induced apoptosis more effectively through a Bak-dependent mechanism. There was an increase in the level of Bcl-xL protein in cells with acquired resistance to Mcl-1 inhibition. Cell lines sensitive to S63845 demonstrated low expression of Bcl-xL. Tumor tissues from patients with lung adenocarcinoma were characterized by decreased Bcl-xL and increased Bak levels of both mRNA and proteins. Concomitant inhibition of Bcl-xL and Mcl-1 demonstrated dramatic cytotoxicity in six of seven studied cell lines. We proposed that co-targeting Bcl-xL and Mcl-1 might lead to a release of Bak, which cannot be neutralized by other anti-apoptotic proteins. Surprisingly, in Bak-knockout cells, inhibition of Mcl-1 and Bcl-xL still resulted in pronounced cell death, arguing against a sole role of Bak in the studied phenomenon. We demonstrate that Bak and Bcl-xL are co-factors for, respectively, sensitivity and resistance to Mcl-1 inhibition.
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