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Anticancer effect of 1,2-epoxy-3(3-(3,4-dimethoxyphenyl)-4H-1-benzopiran-4on) Propane (EPI) and combination with Doxorubicin on HTB183 lung cell cancer culture
Published in Ade Gafar Abdullah, Isma Widiaty, Cep Ubad Abdullah, Medical Technology and Environmental Health, 2020
A.F. Sobandi, R.B. Soeherman, L. Yuniarti, F.A.F. Mansoer
Several in vitro and in vivo studies show the protective effect of genistein from pulmonary carcinogenesis when this compound is used alone or with other compounds (Mahmood et al. 2011, Zhu et al. 2012). Genistein shows anticancer effects on small-cell lung cancer (SCLC) H446; molecules that induce cell-cycle arrest and apoptosis cycles, deregulation of Forkhead box M1 (FoxM1) proteins and their target genes (for example, the 25B cell division cycle (Cdc25B), cyclin B1, and surviving). In A549, genistein lung cancer cells (5–10 mM) increase apoptosis induced by trichostatin A (TSA) and increase expression of TNF receptor 1 TNF receptors (TNFR-1), which mediate the extrinsic apoptotic pathway (Shiau et al. 2010, Wu et al. 2012). If EPI has a structure similar to genistein, EPI allows it to have genistein-like activity against cancer cells. EPI has an anticancer effect on HeLa cervical cancer cells with a mechanism similar to genistein and has anticancer properties through induction of intrinsic pathways and extrinsic apoptosis in tumor cells that vary through inhibition of NF-Kappa β, activation of p53 signaling, activation of p53, and regulation of the formation of Bcl-2 and ROS (Yuniarti et al. 2018).
The Anticancer Potential of the Bacterial Protein Azurin and Its Derived Peptide p28
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Ana Rita Garizo, Nuno Bernardes, Ananda M. Chakrabarty, Arsénio M. Fialho
Experiments with isothermal calorimetry demonstrated that azurin binds to the NH2-terminal domain of p53 with nanomolar affinity in a 4:1 stoichiometry, as well to the DNA-binding domain of this protein [28]. A few studies, supported by site-directed mutagenesis, suggest that a specific region of azurin has been implicated in this complex formation. This region (Met-44 to Met-64) forms a hydrophobic patch and is located within the p28 peptide [32]. Thus, with the inhibition of proteasomal degradation of p53 occurs a raise of the cytoplasmic and nuclear levels of this protein, and consequently, increased DNA binding activity. The levels of the cyclin-dependent kinase inhibitors p21 and p27 also increase, which in turn reduces the intracellular levels of cyclin-dependent kinase 2 (CDK2) and cyclin A1, essential proteins in the mitotic process, as well as Forkhead box M1 (FOXM1), a transcription factor for G2/M progression. Since these components are involved in controlling the cell cycle, the reduction in their levels interrupts this process at the G2/M phase, thus leading to apoptosis (Fig. 9.2; [16]). With this, it was possible to understand that the use of azurin/p28 can be a good therapeutic option for the regression of tumors.
Football and healthy ageing
Published in Peter Krustrup, Daniel Parnell, Football as Medicine, 2019
Pasqualina Buono, Jesper L. Andersen, Andreina Alfieri, Annamaria Mancini, Stefania Orrù, Marie Hagman, Peter Krustrup
Lifelong football training also positively affects the expression of biomarkers involved in DNA repair mechanisms and in senescence suppression pathways, as demonstrated by the increased expression levels of key proteins belonging to these pathways, i.e. p42–44 mitogen-activated protein kinase-MAPK (Erk1/2), AKT serine/threonine kinase 1 (AKT), mammalian target of rapamycin (mTOR) and Forkhead box M1 (FoxM1), in football veterans compared to active untrained age-matched elderly subjects. In particular, the increase of Erk1/2 proteins, which regulate proliferation and differentiation of muscle cells playing an important role in the myogenic response to exercise, is interesting in this context (Park-ington et al., 2004). AKT, which is involved in the growth and hypertrophy of skeletal muscle, could be involved in the senescence suppression pathway, but the mechanisms are not well understood (Bodine et al., 2001; Pallafacchina et al., 2002). Nevertheless, it is interesting that AKT at the protein level was increased in skeletal muscle from football veterans (Mancini et al., 2017), which is in line with another finding obtained in trained versus untrained young subjects (Frosig et al., 2007). mTOR is another crucial regulator of cell growth and longevity pathways (Harrison et al., 2009; Katewa and Kapahi, 2011); its expression was found to be upregulated in skeletal muscle of elderly mice compared with young mice (Lamming et al., 2012). The role of mTOR in human muscle ageing has not been completely elucidated. It regulates protein synthesis in response to environmental stimuli such as nutrients (i.e., amino acid) and growth factors (i.e. insulin and insulin-like growth factor 1) (Li et al., 2012). Similarly to AMPK, mTOR also responds to mechanical stimuli (i.e. muscle contraction) in humans. In fact, some studies have reported that resistance exercise acutely activates AMPK and mTOR signalling (Dreyer et al., 2010; Koopman et al., 2006; Watson and Baar, 2014), but it is not clear whether chronic/long-term resistance training could lead to an activation of these signal cascades. The expression levels of mTOR protein did not show significant changes in muscle from veterans compared to active untrained elderly subjects, as reported in Mancini et al. (2017), which is in line with a previous study indicating no variation in mTOR protein expression in muscle from active and sedentary young and elderly subjects, probably due to high interindividual variability (Sandri et al., 2013). FoxM1 transcription factor regulates several biological functions, including cell proliferation, cell cycle progression and differentiation, playing a pivotal role in the senescence suppression pathway and in DNA repair mechanisms (Behrens et al., 2014). Increased FoxM1 transcription factor expression has been associated with senescence suppression (Bella et al., 2014); both FoxM1 mRNA and protein expression levels were increased in muscle from veterans compared to untrained elderly subjects (Mancini et al., 2017).
FoxM1 Regulates Proliferation and Apoptosis of Human Neuroblastoma Cell through PI3K/AKT Pathway
Published in Fetal and Pediatric Pathology, 2022
Junzuo Liao, Lin Jiang, Cheng Wang, Dan Zhao, Wenfei He, Kejun Zhou, Yun Liang
FoxM1 is a proliferation-specific transcriptional factor, belongs to the Fork head Box (Fox) superfamily of transcriptional factors, also known as fork head homolog 11 (HFH-11), hepatocyte nucleus factor 3 (HNF-3), membrane protein palmitoylated 2 (MPP2), Trident or WIN [4]. In normal tissues, FoxM1 is expressed during embryogenesis and in progenitors with extensive proliferating capacity. The expression is diminished in terminally differentiated cells or resting cells [5]. Its expression is strongly correlated with the proliferation capacity of the cells. Therefore, FoxM1 overexpression is also crucial for the development and progression of many types of human malignancies [6], including NB. Zebin et al. found that FoxM1 is involved in promoting tumorigenesis and metastasis by maintaining the undifferentiated state of aggressive NB cells [7]. Therefore, FoxM1 is an attractive focus for anticancer research.
Novel insights into the pathogenesis of virus-induced ARDS: review on the central role of the epithelial-endothelial barrier
Published in Expert Review of Clinical Immunology, 2021
Jun Feng, Lina Liu, Yang He, Min Wang, Daixing Zhou, Junshuai Wang
Likewise, the pulmonary endothelium has substantial regenerative capacity, and lineage tracing suggests that the native endothelium is the source of microvascular repair after influenza injury. The endothelium may also contribute to tissue repair after viral infection by stimulating nearby epithelial cells by secreting growth factors or barrier-protecting proteins, such as thrombospondin-1, matrix metalloproteinase-14 and hepatocyte growth factor [86]. Endothelial regeneration is primarily accomplished by migration and proliferation of resident endothelial cells. The transcription factor FoxM1 plays a critical role in regulating endothelial cell proliferation and regeneration after inflammatory vascular injury [9,87]. However, uncontrolled epithelial cell proliferation and impaired tissue repair during the later stages of viral infection can induce ARDS and lead to pulmonary fibrosis [19]. Severe respiratory failure caused by avian influenza H7N9 virus infection is attributed to histological alteration of organizing pneumonia (OP), which was confirmed by the existence of intraluminal plugs of granulation tissue within alveolar ducts and surrounding alveoli associated with chronic inflammation of the surrounding lung parenchyma [88,89]. Thus, the impairment of epithelial-endothelial repair contributes to the development of ARDS.
WHSC1 promotes wnt/β-catenin signaling in a FoxM1-dependent manner facilitating proliferation, invasion and epithelial-mesenchymal transition in breast cancer
Published in Journal of Receptors and Signal Transduction, 2020
Jinfan Zhang, Jingyu Lu, Yu Chen, Hang Li, Lisheng Lin
To explore the function mechanism of WHSC1, we transfected pcDNA3.1-NC and pcDNA3.1-WHSC1 plasmids into MDA-MB-231 cells to overexpress WHSC1. First, we performed qPCR to detect the mRNA expression levels of WHSC1. Result showed that compared with control, WHSC1 was overexpressed in MDA-MB-231 cells transfected with pcDNA3.1-WHSC1 (Figure 4(A)). Recent studies have reported that the transcription factor FoxM1 plays a vital function in tumorigenesis. Then we detected the protein accumulation of FoxM1 in WHSC1 knockdown or overexpressed MDA-MB-231 cells. Western blot showed that overexpression WHSC1 could increase FoxM1 expression, but knockdown of WHSC1 could decrease FoxM1 expression (Figure 4(B)). IHC was also carried out to detect the expression of FoxM1 in tumor tissues. Results showed that the accumulation of FoxM1 was higher in breast cancer tissues than that in normal breast tissue (Figure 4(C)). Taken together, these result suggested that WHSC1 regulates the expression of FoxM1 in BC cells and tissues.