China
Africa
Explore chapters and articles related to this topic
Mechanisms of Different Anticancer Drugs
Published in Anjana Pandey, Saumya Srivastava, Recent Advances in Cancer Diagnostics and Therapy, 2022
Anjana Pandey, Saumya Srivastava
Venetoclax is a novel anticancer compound that blocks the antiapoptotic Bcl-2 protein from programmed cell death (Roberts and Huang, 2017). It showed promising results in AML patients in combination with azacitidine and scientists are hoping that it will also be effective for other cancer types in the future. More prolonged survival and reduction in incidence were observed compared to those treated with azacitidine alone (DiNardo et al., 2020). Apart from the stimulation of G1/S transition gene expression, E2F also induces the proapoptotic gene expression. However, many tumor cells can develop signaling pathways to avoid cell death, countering the E2F. These cancer-shielding unique pathways are targets for novel treatments. p53 is the most crucial tumor suppressor protein involved in apoptosis. More than 50% of cancers have mutated p53 genes (Schmitt et al., 2002).
Resistance Mechanisms of Tumor Cells
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Fortunately, there are several drugs available (e.g., CP-31398, PRIMA-1, ARP-246, MIRA-1, STIMA-1, a.o.) that selectively bind to distinct TP53 mutants and partially restore their activity, or, inhibit at least the TP53 interactions with other proteins (e.g., TP73; Blandino and Di Agostino, 2018; Bykov et al., 2018). For most of these drugs, it has been demonstrated by in vitro—and in some cases also by in vivo experiments—that they are highly potent to re-sensitize tumor cells that bear different types of p53 mutations. Future studies will unravel the power of restoring TP53 activity in tumor cells, but all experimental evidence looks quite promising, and hopefully these drugs will quickly enter larger clinical trials to circumvent the deleterious effects of TP53 mutations.
Glossary of scientific and technical terms in bioengineering and biological engineering
Published in Megh R. Goyal, Scientific and Technical Terms in Bioengineering and Biological Engineering, 2018
p53 gene is also known as tumor protein p53, p53, cellular tumor antigen p53, phosphoprotein p53, or tumor suppressor p53. It is a protein that is encoded by the TP53 gene. The p53 protein is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor, preventing cancer. As such, p53 has been described as “the guardian of the genome” because of its role in conserving stability by preventing genome mutation. Hence TP53 is classified as a tumor suppressor gene. The name p53 is in reference to its apparent molecular mass: SDS-PAGE analysis indicates that it is a 53-kilodalton (kDa) protein. However, based on calculations from its amino acid residues, p53’s mass is actually only 43.7 kDa. This difference is due to the high number of proline residues in the protein; these slow its migration on SDS-PAGE, thus making it appear heavier than it actually is. It is a human tumor-suppressor transcription factor gene, damage or mutation to which is believed to be responsible for up to 60% of all human cancer tumors. If, in spite of the presence of p53 protein, a cell begins to divide uncontrollably following damage to its DNA, the p53 gene acts to prevent tumors by triggering apoptosis.
Oxidative stress links the tumour suppressor p53 with cell apoptosis induced by cigarette smoke
Published in International Journal of Environmental Health Research, 2022
Qing Song, Zi-Jing Zhou, Shan Cai, Yan Chen, Ping Chen
The tumor-suppressor protein p53 is a key regulator of cell apoptosis. There were studies showed that the expression level of p53 protein in lung tissue and airway epithelial cells was significantly up-regulated (Siganaki et al. 2010; Gogebakan et al. 2014). Damico et al. (2011) findings showed that after exposure of human pulmonary macrovascular endothelial cells to CSE, the p53 protein expression was significantly increased which was related to cell apoptosis. However, macrophage migration inhibitory factor could protect human vascular endothelium from the toxic effects of CSE via the antagonism of p53-mediated apoptosis. Similar results were observed in our study. In the lung tissue of mice exposed to CS, the protein expression of p53 and alveolar septal cell apoptosis were increased. Also, the expression of pro-apoptotic protein Bax, total caspase-3 and cleaved caspase-3 were increased, while the expression of anti-apoptotic protein Bcl-2 was decreased. However, inhibited expression of p53 could significantly reduce apoptosis, decrease the protein expression of Bax, total caspase-3 and cleaved caspase-3, while increase expression of Bcl-2. It implied that p53 mediates cigarette smoke-induced apoptosis and participates in the development of emphysema.
Polyphenon-E encapsulated into chitosan nanoparticles inhibited proliferation and growth of Ehrlich solid tumor in mice
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Azza I. Othman, Ibrahim M. El-Sherbiny, Mohamed A. ElMissiry, Doaa A. Ali, Engy AbdElhakim
The prime pathway followed by cancer cells is to suppress apoptosis and p53 function; therefore appropriate anticancer treatments would stimulate apoptotic mechanisms and regain p53 activity to inhibit cancer proliferation. Apoptosis consists of mitochondrial and transmembrane death receptors pathways which comprise of the activation the effector caspases via the initiator caspases in cell death [32]. Consistent with increased expression of p53 in Ehrlich tumor of mice treated with CSNPS-PE, there was greater activation of CD96, caspases 3, 8 and 9 with up-regulation of Bax and down-regulation of Bcl-2 compared to free PE and void CSNPs. Changes in the Bax to Bcl-2 ratio resulted in the destabilization of the mitochondrial membrane and liberation of the proteolytic caspases and cleavage of PARP [33] that lead to cell death [3].
Exposure to long-term evolution radiofrequency electromagnetic fields decreases neuroblastoma cell proliferation via Akt/mTOR-mediated cellular senescence
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Ju Hwan Kim, Sangbong Jeon, Hyung-Do Choi, Jae-Hun Lee, Jun-Sang Bae, Nam Kim, Hyung-Gun Kim, Kyu-Bong Kim, Hak Rim Kim
Generally, in response to DNA damage, p53 might act as a transcription factor for tumor suppression, and play a crucial role in the regulation of the cell cycle and apoptotic progression to preserve genomic stability (Speidel 2015; Yogosawa and Yoshida 2018). However, in the absence of DNA damage, the Akt/mTOR pathway is activated and promotes accumulation of p53 and p21 (Astle et al. 2012). Akt induces cellular senescence, which activates mTOR; mTOR subsequently competes with MDM2, a negative regulator of p53, and prevents p53 degradation and stabilizes p53 (Astle et al. 2012; Jung et al. 2019). Further, mTOR directly activates p53, which might account for how sustained Akt activity might alter the cell fate to premature senescence (Jung et al. 2019).