Cancer Biology and Genetics for Non-Biologists
Trevor F. Cox in Medical Statistics for Cancer Studies, 2022
When a cell divides into two daughter cells, it passes through two gap phases (G1 and G2), a synthesis phase (S) and a mitosis phase (M). A brief description of the phases is: G1 phase: the cell enlarges, organelles are copied, preparation for cell divisionS phase: DNA replicatesG2 phase: the cell further enlarges, proteins and organelles are madeM phase: the splitting of the cell, first mitosis consisting of the phases: prophase, metaphase, anaphase and telophase, followed by cytokinesis where the cytoplasm of the cell is split in two, resulting in the two new cells
Melatonin: A “Guardian” of the Genome and Cellular Integrity for Prevention of Photocarcinogenesis
Andreia Ascenso, Sandra Simões, Helena Ribeiro in Carrier-Mediated Dermal Delivery, 2017
One of the most important tumor suppressor genes is p53- gene, which is often called the “guardian of the genome” and is located on chromosome 17p [94,101,107,115,116]. In fact, the mutation of p53-gene is the most dangerous UV damage by disabling the cells to inhibit the cancer development [94]. UV acute exposure up-regulates the transcription of this crucial gene resulting in an increase of p53 protein production. This protein permits to restore the damaged DNA by stopping the cell cycle in G1 phase prior to its incorrect replication in next phases [94]. If the damage is too extensive and this repair mechanism is not possible, the cell has another important repairing mechanism which is represented by the apoptosis process. This programmed cell death occurs through the action of the tumor suppressor gene (p53-gene) or due to the activation of death receptors and the subsequent activation of the caspases cascade [94].
Introducing Molecular Biology of Head and Neck Cancer
John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford in Head & Neck Surgery Plastic Surgery, 2018
RB was the first TSG to be identified and any treatise on the RB gene will usually include mention of Alfred Knudsen, retinoblastoma, and the two-hit hypothesis that he proposed.84, 116, 117RB functions to regulate the G1-S phase transition of the cell cycle and it does this by binding to and inhibiting the activity of a family of transcription factors called E2Fs. As the cell enters the cell cycle at the G1 phase in response to mitogenic signalling (see Figure 6.4), the signal passes intracellularly from the activated transmembrane receptor molecules at the cell surface to promote the transcription of cyclins. (Mitogenic signals are induced by mitogens: factors that stimulate mitosis such as growth factors e.g. epidermal growth factor (EGF).) Cyclins that are produced then bind to cyclin-dependent kinases (CDKs) that perform phosphorylation reactions targeting a range of genes, one of these being RB.84 Phosphorylation of RB leads to inactivation of RB since it no longer binds to E2F and as a result, E2Fs promote transcription of their target genes, which inter alia includes genes involved in DNA synthesis i.e. S-phase (see Figure 6.4). As a consequence, RB not only regulates the cell cycle, but also regulates the cell cycle arrest that is a requirement for terminal differentiation (which is frequently regulated by RB related proteins p107 and p130).118, 119
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.
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.