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The Fight Against Cancer
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Abnormalities in cell cycle regulation may occur at any of the four major phases, known as G1, S, G2, and M. progression through these phases of the cell cycle depends on the balance of the chemical signals that promote growth or inhibition. The G1 (gap 1) phase is where the cell grows in size and prepares for DNA replication in response to growth factors. The second phase (synthesis) is when DNA replication takes place. The next interval, once the chromosomes have been copied, is G2 phase (gap 2) where the cell prepares for division. During this interval, the cell has time to check for errors in the DNA replication, and repair any damaged copies. The final phase, M (mitosis) is when cell division happens to produce two daughter cells, each containing a full set of chromosomes. The daughter cell then begins the cell cycle at the G1 phase, or may remain in a dormant phase G0.
Colon cancer: pathology and natural history
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
The overexpression of full-length APC protein blocks cell cycle progression from the G0/G1 to the S phase19, presumably by the inhibition of cyclin-dependent kinase-2 activity, although the exact mode of action of APC in cell cycle regulation is still unclear. Loss of functional APC could result in impairment of cell migration, perhaps as a result of stabilization of cell-cell adhesions due to an increase of E-cadherin-catenin units. A simultaneous increase in cell proliferation could further enhance accumulation of cells at the crypt-villus boundary and result in polyp formation, setting the stage for carcinogenesis.
Introducing Molecular Biology of Head and Neck Cancer
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Nikolina Vlatković, Mark T. Boyd
Cyclin D1 is the protein encoded by the CCND1 gene and this gene has frequently been found to be amplified in a range of cancers including head and neck cancers.18, 123–125 Cyclins are the critical regulators of the cell cycle and are typically short-lived proteins that are regulated transcriptionally.126, 127 In the case of cyclin D1, expression is regulated by the MAPK pathway, which is activated following receptor mediated tyrosine kinase activation, by for example, growth factors (EGF binds to the EGF receptor EGFR, see Figure 6.4), cyclin D1 associates with cyclin dependent kinases 4 and 6 to promote phosphorylation of target proteins, in particular of the RB TSG leading to its inactivation and cell cycle progression. Thus, gene amplification of CCND1 provides for constitutively increased cyclin D expression and loss of normal cell cycle regulation at the G1-S checkpoint.128 let-7c is a microRNA (miRNA) that regulates a number of target genes and that has been found to be down-regulated/deleted in approximately 40% of HPV− head and neck cancers and this was associated with increased CDK6 expression, anticipated to promote cell cycle progression in combination with CCND1.
The role of CSE1L silencing in the regulation of proliferation and apoptosis via the AMPK/mTOR signaling pathway in chronic myeloid leukemia
Published in Hematology, 2023
Xiao-Yu Liu, Yong-Hong Wang, Jing Wang, Ji-Kun Quan, Xu-Dong Li, Kun-Ping Guan
CSE1L has been reported to play an important role in maintaining the balance between cell proliferation and apoptosis [6,28]. Cancer development and survival need CSE1L [29]. Inhibition of CSE1L expression has been shown to slow the growth and spread of triple-negative breast cancer [30]. Silencing CSE1L inhibits the viability of lung cancer cells and reduces malignant transformation of cancer cells [31]. However, no studies on the expression of CSE1L in CML have been done. To investigate the possible molecular mechanism of CSE1L expression in CML patients, we detected the relative expression level of CSE1L in bone marrow granulocytes by flow cytometry. The results showed that strong CSE1L signals were detected in bone marrow granulocytes from patients with primary CML. In a K562 cell model,we showed that knockdown of CSE1L shifts K562 cells from low Annexin to medium Annexin levels. This result confirmed that knockdown of CSE1L can reduce the growth of K562 cells and induce apoptosis. Disruption of cell cycle checkpoints has been identified as a hallmark of cancer, with the G1-S phase being the most important regulatory point in cell cycle regulation [32,33]. In our study, knockdown of CSE1L also hindered the cell cycle transition from G0/G1 phase to the S phase, without significant effect on the G2/M phase. Interestingly, our study showed that imatinib triggered a downregulation of CSE1L in K562 cells. The results suggest that CSE1L is involved in imatinib-induced killing of K562 cells. The findings suggest that CSE1L may play a significant role in the onset and progression of CML.
Combined Network Pharmacology and Cytology Experiments to Identify Potential Anti-Breast Cancer Targets and Mechanisms of Delphinidin
Published in Nutrition and Cancer, 2022
Jiayuan Peng, Ailin Wu, Xiaoping Yu, Qian Zhong, Xiaoming Deng, Yanfeng Zhu
Early research confirmed that the anticancer activities of anthocyanins can suppress the initiation, promotion, and progression of breast cancer (26–29). Our team found that black rice-derived anthocyanins inhibited breast cancer cell proliferation and migration (30). An anthocyanin-rich fruit extract can also significantly reduce the vitality of breast cancer MCF-7 cells (31). In breast cancer cells that are ER-positive, HER2 overexpressing and triple negative, delphinidin reduces proliferative activity and promotes apoptosis by down-regulating the ERK1/2 signaling pathway (32). Similarly, in our experimental, delphinidin has been found to selectively show cytotoxicity to MCF-7 and BT-474 cells and significantly inhibit the proliferation and adhesion of breast cancer cells. Cell cycle regulation is important in cancer therapy. Recent studies confirmed that the anthocyanin-rich extract from Aronia melanocarpa induced G1/G0 and G2/M cell cycle arrest in colon cancer cells HT-29 by increasing the p21WAF1 and p27KIP1 expression and decreasing cyclin A and cyclin B expression (33). Similarly, Tsai et al. demonstrated that anthocyanidin extract can arrest the cell cycle of G2/M phase transition in p53-deficient leukemia HL-60 cells (34). Our pathway-enrichment results predicted that the anti-breast cancer of delphinidin mainly affects cell cycle regulation, and cytological experiments demonstrated that delphinidin can induce G2/M cell cycle arrest in breast cancer MCF-7 and BT-474 cells and may be involved in apoptosis induction.
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.