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Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
Due to their pivotal role in tumorigenesis, metastatic spread and drug resistance, several strategies have been developed by various investigators to inhibit HDACs in cancer cells (Li and Seto, 2016). Mechanistically, inhibition of HDAC enzymes using pharmacological agents arrests cell growth, promotes cell differentiation and induces apoptosis (Eckschlager et al., 2017). Reduction of HDAC activity promotes the expression of apoptotic proteins such as p53, Bax, Caspases and poly (ADP-ribose) polymerase (PARP) and the cell cycle inhibitors p21 and p27, while down-modulating cyclin D1 and cyclin B2 (Uo et al., 2009). Furthermore, targeted inhibition of HDACs promotes RAD-52 and ATM (serine/threonine kinase), thereby increasing cellular oxidative stress (Zhang et al., 2020). Realizing the importance of targeting HDAC proteins, several pharmacological industries have produced synthetic and naturally occurring inhibitors to mitigate HDACs (Singh et al., 2018).
Regulation of Cell Functions
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Analysis of Xenopus laevis oocytes has greatly contributed to a better knowledge of the biochemistry of cell division.321 The cdc2 protein of Xenopus laevis eggs is an essential component of the MPF, a cytoplasmic inducer of mitosis that is composed of cdc2 and cyclin.322 The kinase activity of the cdc2 protein oscillates during the cycle of Xenopus laevis cells, and maximal activity correlates with the dephosphorylated state of the cdc2 protein.323 The protein kinase encoded by the c-mos proto-oncogene is required for MPF activation and mouse oocyte maturation.324 The c-Mos serine/threonine kinase directly phosphorylates the cyclin B2 component of MPF.
Herbal Products for the Treatment of Psoriasis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Anna Herman, Andrzej P. Herman
Psoriasis is typically characterized as inflamed skin with surface scale and thickening of the epidermis (acanthosis or reduction or absence of the granular layer) caused by parakeratosis, which is a consequence of nuclei retention in stratum corneum keratinocytes caused by abnormal differentiation and hyperproliferation of epidermal keratinocytes (Johnson-Huang et al. 2012). Therefore, a number of studies have shown that inhibition of keratinocyte hyperproliferation, induction of their apoptosis, and modulation keratinocyte differentiation may be considered targets of antipsoriatic strategies. Animal-based studies support the efficacy of the herbal products for the treatment of psoriasis via inhibition of keratinocyte hyperproliferation. The ethanolic extract of A. vera leaf gel (Dhanabal et al. 2012) and the ethanolic extract of N. sativa seeds (Dwarampudi et al. 2012) produced a significant epidermal differentiation seen as orthokeratosis when compared with the control group and tazarotene (0.1%) gel, respectively. However, the most desirable herbal products for psoriasis treatment are ones that inhibit epidermal hyperplasia and inflammation simultaneously. Tuhuai extract (Man et al. 2008) and baicalin isolated from S. baicalensis (Wu et al. 2015) reduced epidermal hyperplasia and inflammation in mice, which makes them valuable drugs for the treatment of psoriasis. Moreover, 5% baicalin cream promotes epidermal differentiation and normal keratinization of keratinocytes in mouse skin, similar to that seen with 0.1% tazarotene cream (Wu et al. 2015). Flavonoid quercetin from the rhizome of S. china shows significant orthokeratosis, reduction in epidermal thickness, and anti-inflammatory and maximum antiproliferant activities compared with mice treated with retinoic acid (Vijayalakshmi et al. 2012). PSORI-CM01 (C. zedoaria, S. glabra, Dark Plum Fruit, Rhizoma Smilacis Glabrae, L. erythrorhizon, P. lactiflora, and G. uralensis) inhibits epidermal hyperplasia in the imiquimod-induced mouse psoriasis-form model and reduces keratinocyte proliferation in vitro through downregulation of cyclin B2 (Wei et al. 2016). Herbal product treatment of psoriasis through inhibition of the keratinocyte hyperproliferation was also confirmed in clinical studies. I. naturalis ointment modulates the proliferation (decreased proliferating marker Ki-67) and differentiation of keratinocytes in epidermis (increased levels of filaggrin), as well as inflammatory reactions by inhibiting the infiltration of T lymphocytes (decreased inflammatory marker CD3) in patients with chronic plaque psoriasis (Lin et al. 2007). Moreover, I. naturalis, as well as its major active constituent induribin, inhibited proliferation and abnormal differentiation of epidermal keratinocytes through decreased proliferating cell nuclear antigen (PCNA) and increased involucrin at both the mRNA and protein levels in patients with psoriatic lesions (Lin et al. 2009).
CircPTK2 promotes cell viability, cell cycle process, and glycolysis and inhibits cell apoptosis in acute myeloid leukemia by regulating miR-582-3p/ALG3 axis
Published in Expert Review of Hematology, 2022
Zhen Shang, Xi Ming, Jiaying Wu, Wanying Liu, Yi Xiao
Subsequently, the underlying mechanism of circPTK2 in the regulation of AML development was investigated. We demonstrated that circPTK2 could positively modulate ALG3 expression through miR-582-3p adsorption. MiR-582-3p level was declined in AML patients and AML cells and negatively correlated with circPTK2 level. Moreover, miR-582-3p suppression reversed the impacts of circPTK2 knockdown on AML cell malignant phenotypes, indicating that circPTK2 altered AML progression by sponging miR-582-3p. Upregulation of miR-582-3p restrained cell viability, cell cycle process, and glycolysis and induced apoptosis in AML cells. In support of our findings, Li et al. uncovered that miR-582-3p was lowly expressed in leukemia patients and cell lines, and its elevation suppressed cell growth and cell cycle process in AML cell lines via binding to cyclin B2 [20]. In addition, ALG3 level was related to the overall survival of AML patients and altered the development of chemoresistance in AML via the lncRNA FTX/miR-342/ALG axis [28]. However, we were the first to explore the interaction between miR-582-3p and ALG3 in AML. Of note, we found that the elevation of ALG3 could effectively ameliorate the impacts of miR-582-3p on the malignant biological phenotypes of AML cells, which indicated that miR-582-3p inhibited AML cell progression by targeting ALG3.
Genetic variations as molecular diagnostic factors for idiopathic male infertility: current knowledge and future perspectives
Published in Expert Review of Molecular Diagnostics, 2021
Mohammad Karimian, Leila Parvaresh, Mohaddeseh Behjati
A study in 2000 by Baudat et al. showed that disruption of Spo11 in mice has led to severe gonadal abnormalities owing to defective meiosis and apoptosis of spermatocytes during the initial prophase. Eggs reach the diplotene/dictyate stage almost normally, but most of them die immediately after birth. Spo11-/- myocytes also showed synaptic defects of homologous chromosomes [84]. In another study, it was found that deletion of Spo11 caused significant changes in the expression of genes involved in meiosis recombination (Hop2, Brca2, Mnd1, FancG) and at the miotic checkpoints (cyclin B2, Cks2) without any impact on the genes encoding the protein components of the synaptonemal complex. Finally, they discovered unknown genes that are affected by the Spo11 disrupted gene that could therefore be specifically involved in meiosis and spermatogenesis [85]. The details of the important genetic polymorphisms of the aforementioned genes as well as some characteristics including pathological effects, sample size, and ethnicity of the studied population are summarized in Table 1.
Cytotoxic, genotoxic, and toxicogenomic effects of dihydroxyacetone in human primary keratinocytes
Published in Cutaneous and Ocular Toxicology, 2021
Anneliese Striz, Ana DePina, Robert Jones, Xiugong Gao, Jeffrey Yourick
We further performed gene ontology analysis to investigate the functional classes affected by 5 mM DHA after 24-h exposure. DEGs with fold change ≥2 and FDR ≤ 0.05 were analyzed in DAVID to identity GO terms in the biological process (BP) category (GOTERM_BP_FAT) as described in the methods. The resulting GO terms were further categorized using the CateGOrizer tool. For the DEGs of DHA exposed NHEK cells compared to control cells, 380 GO terms were identified and grouped into 27 classes within the predefined set of parental GO terms (Figure 4). The most represented functional classes impacted by 24-h DHA exposure were cell organization and biogenesis, cell cycle, and metabolism at 14.74, 13.16, and 12.79% of total GO terms respectively (Figure 4). Canonical pathway analysis using IPA software specifically identified “Cell Cycle: G2/M DNA Damage Checkpoint Regulation” as a top canonical pathway. This pathway revealed eight associated DEGs including aurora kinase A, BRCA1, cyclin B1, cyclin B2, CDC25C, CDK1, CKS2, and TOP2A (Figure 5(A)). All eight of the associated DEGs were significantly down-regulated (Figure 5(B,C)). Particularly, and in agreement with previously published studies10,12, cyclin B1 and CDK1 were significantly decreased 56.33% and 70.59%, respectively, after 5 mM DHA exposure for 24 h (Figure 5(C)).