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Introduction to Cancer
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Furthermore, cells are the most radiosensitive in the late M and G2 phases, and the most resistant in the late S-phase. For cells with a longer cell-cycle time and a significantly longer G1 phase, there is a second peak of resistance late in G1. In the case of radiotherapy, the pattern of resistance and sensitivity correlates with the level of thiol-containing compounds in the cell. Thiols are natural radioprotectors, and tend to be at their highest levels in S-phase and at their lowest near mitosis.
Hormone Receptors and Endocrine Therapy in Breast Cancer
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Sherry X. Yang, Nancy E. Davidson
A significant development in the treatment of metastatic disease is hormonal agent(s) in combination with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor as a type of endocrine-based therapy. Among the mechanisms of endocrine resistance, dysregulation of the cyclin D1-dependent kinase CDK4/6-INK4-Rb-E2F pathway has been shown to correlate with poor response to endocrine therapy (Section 5.5). The CDK4/6 in complex with cyclin D1 phosphorylates the tumor-suppressor protein Rb and eventually leads to progression of the cell-cycle from the G1 phase to S phase. Because CCND1 gene (that encodes cyclin D1) amplification is frequent and cyclin D1 is an ER-target gene, suppression of the cyclin D-mediated CDK4/6 activity is a viable therapeutic intervention in breast cancer and in breast cancer with resistance to endocrine therapy.
Gene Therapy for Lung Cancer
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Choon Taek Lee, David P. Carbone
Other tumor suppressor gene replacements have also been used therapeutically. These include the retinoblastoma protein (Rb), which is mutant in the majority of small-cell lung cancer and about 20% of non-small-cell lung cancer (74,75). Rb introduction has definite antitumor effects, which appear to depend on the extracellular environment of the tumor (76). A p53-inducible inhibitor of cyclin-dependent kinases, WAF/CIP1, is another candidate gene for the replacement therapy (77). A large part of the growth regulatory action of p53 appears to be mediated by this protein, also known as p21. Overexpression of these two genes can arrest the cell cycle in G1 phase (77). Adenovirusp21 therapy of p53-deleted mouse prostate cancer cell lines induced growth arrest and resulted in a reduction of Cdk-2 kinase activity. And intratumoral injection with adenovirus-p21, but not with adenovirus-p53, prolonged the survival of tumor-bearing mice (78,79). Inhibitory activity was also found in human non-small-cell lung cancer cell lines (80).
Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Mona S. El-Zoghbi, Samiha A. El-Sebaey, Hanan A. AL-Ghulikah, Eman A. Sobh
The cell cycle is required for cell division and replication. The cell cycle was divided into four distinct phases: G1 phase (synthesis), S phase (synthesis), G2 phase (interphase), and M phase (mitosis). The G1 phase, also known as the post-mitotic pre-synthesis phase, is distinguished by direct cell division. DNA replication identifies the S phase. The G2 phase, premitotic, or post-synthetic phase, which can be considered the actual division, is when the cell prepares to split into two cells. Finally, the doubled DNA organised in chromosomes is separated during the M- or mitosis-phase division25. Many anticancer drugs cause apoptosis, cell cycle arrest, or a combination of both as part of their cytotoxic action52. As a result, it was worth investigating whether cell cycle arrest was involved in the cytotoxicity mechanism of the most active cytotoxic agent 4c on A549 cells using flow cytometry analysis, and the results were demonstrated in Table 4 and Figure 7. The results revealed a 69.07% increase in cell count at the G0-G1 phase, compared to 56.39% for control cells. While the percentage of cells in the S phase was reduced by 26.89% compared to the control (29.64%). On the other hand, a dramatic fall in the cell population in the G2/M phase was observed upon treatment with compound 4c from 13.97 to 4.04%. As a result, compound 4c was demonstrated to significantly disrupt the cell cycle profile and cause cell cycle arrest.
Therapeutic potential of a 2,2’-bipyridine-based vanadium(IV) complex on HepG2 cells: cytotoxic effects and molecular targeting
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Eman Salah El-Shafey, Eslam Samy Elsherbiny
Several genes that control cell growth, apoptosis, cell migration and cell cycle mediate cellular propagation of HCC cells [33]. Uncontrolled progression of cells is a lineament property of cancer, including HCC [34]. In this study, cells were accumulated G0/G1 phase (47.5%). It was reported that the main monitoring events resulting in cellular propagation happen in the G1 phase involved the dramatic expression of cyclins and cyclin-dependent kinases (CDKs) [35]. Increased levels of cyclin D1 protein as cell cycle regulator are associated with aggressive forms of HCC via the stimulation of TGF‐β/Smad signaling pathway [36,37]. In this study, HepG2 cells showed overexpression of cyclin D1 gene expression that leads to G1 and S phase progression and is involved in sustaining HCC cancer cell proliferation.
GC-MS Profiling and Antineoplastic Activity of Pelargonium Inquinans Ait Leaves on Acute Leukaemia Cell Lines U937 and Jurkat
Published in Nutrition and Cancer, 2022
Ogochukwu Izuegbuna, Gloria A. Otunola, Graeme Bradley
Cell cycle regulation was also investigated in this study. The extracts of Pelargonium inquinans were observed to cause G1 cell cycle arrest in both Jurkat and U937 cell lines. This is related to similar findings in P. sidoides by Perreira et al20. The G1 phase is usually characterized by protein synthesis toward cell division. In a recent study, cancer cells were observed to migrate more rapidly in the G0/G1 phase than in the S/G2/M phase; they were also more resistant to cytotoxic drugs in the G0/G1 phase21. Thus targeting the G1 phase of the cell cycle is seen as a viable option in cancer management22. Flavopiridol, a flavonoid, and a pan-CDK inhibitor showed significant activity in chronic lymphoid leukemia, though with overt toxicities23. Cell cycle progression in the G1 phase is regulated by CDK 4 and six and palbociclib a CDK4/6 inhibitor have been shown to have activity in acute myeloid leukaemia24. A Phase I/II clinical trial of palbociclib and CPX-351 is currently ongoing (NCT03844997). Dinaciclib a CDK9 inhibitor that also promotes apoptosis in MLL-rearranged AML is also currently being evaluated with some other drugs in AML in some clinical trials (NCT03484520); (NCT02684617). Thus, cell cycle inhibitors can be viable options in the management of AML.