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- Fares, M, et al.
(författare)
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COL-3-Induced Molecular and Ultrastructural Alterations in K562 Cells
- 2022
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Tetracycline-3 (4-dedimethylamino sancycline, COL-3) is a non-antibiotic tetracycline derivative. COL-3 exerts potent anti-metalloproteinase activity and its antitumor effects have been reported both in vitro and in vivo. In this study, we investigated the mechanisms of COL-3-induced cytotoxicity in a chronic myeloid leukemia cell line, K562, characterized by the BCR–ABL fusion protein. COL-3 induced K562 cell death in a concentration-dependent manner with an IC50 of 10.8 µg/mL and exhibited features of both apoptosis and necrosis. However, flow cytometry analysis revealed that necrotic cells dominated over the early and late apoptotic cells upon treatment with COL-3. Transmission electron microscopy analysis in combination with Western blotting (WB) analysis revealed early mitochondrial swelling accompanied by the early release of cytochrome c and truncated apoptosis inducing factor (tAIF). In addition, ultrastructural changes were detected in the endoplasmic reticulum (ER). COL-3 affected the levels of glucose-regulated protein-94 (GRP94) and resulted in m-calpain activation. DNA double strand breaks as a signature for DNA damage was also confirmed using an antibody against γH2AX. WB analyses did not demonstrate caspase activation, while Bcl-xL protein remained unaffected. In conclusion, COL-3-induced cell death involves DNA damage as well as mitochondrial and ER perturbation with features of paraptosis and programmed necrosis.
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- Zhao, Y, et al.
(författare)
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Cardiovascular Complications in Hematopoietic Stem Cell Transplanted Patients
- 2022
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many patients suffering from hematologic malignancies, solid tumors, inborn errors of metabolism or genetic disorders. Despite decades of successful HSCT, clinical outcomes are still far from satisfactory due to treatment-related complications, including graft-versus-host disease (GvHD) and cardiovascular complications (CVC). CVC may affect patients in the acute period post-HSCT; however, the occurrence is far higher among long-term survivors. Induction treatment using cardiotoxic treatments, e.g., anthracyclines and radiotherapy, conditioning regimens containing cyclophosphamide, and post-HSCT comorbidities, including GvHD, are factors contributing to CVC. Cardiac function evaluation prior to and post-transplantation is an important strategy for choosing the proper conditioning regimen, HSCT protocol and post-HSCT supportive care. Cardiac systolic function evaluation by echocardiography, in addition to serum cardiac biomarkers, such as troponins and brain natriuretic peptides, is recommended as a routine follow-up for HSCT patients. Angiotensin-converting enzyme inhibitors, angiotensin-II-receptor blockers, and beta-blockers, which are mostly used for the treatment of chemotherapy-induced cardiotoxicity, might be used as treatments for HSCT-related CVC. In summary, the present review reveals the urgent need for further investigations concerning HSCT-related CVC both at the preclinical and clinical levels due to the lack of knowledge about CVC and its underlying mechanisms.
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