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Garcinia indica (Kokum) and Ilex aquifolium (European Holly)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Dicson Sheeja Malar, Mani Iyer Prasanth, Tewin Tencomnao, James Michael Brimson, Anchalee Prasansuklab
In a dose-dependent manner, UA inhibits the invasive property of renal carcinoma and gastric cancer cells through the activation of NLRP3 inflammasome (Chen et al., 2020b; Chen et al., 2020c). UA activates Hippo pathway (Mst1/2, WW45, LATS1/2, Yap, and Mob1) via Rassf1 to inhibit invasion, migration and induce apoptosis in gastric cancer cells (Kim et al., 2019b). In addition, through the downregulation of Axl/NF-κB pathway, UA inhibits the epithelial-mesenchymal transition in inhibiting the migration of gastric cancer cells (Li et al., 2019). UA induces the generation of ROS thereby downregulating the survival-dependent genes and metastasis genes to cause apoptosis in intestinal cancer cells (Rawat and Nayak, 2021).
Focusing on Hippo Pathway in Stem Cells of Oral Origin, Enamel Formation and Periodontium Regeneration
Published in Organogenesis, 2022
Tianyi Wang, Kehan Li, Hanghang Liu, En Luo
Since first discovered in Drosophila, Hippo pathway has been drawing interest in regulation on cell proliferation, migration and apoptosis.1,2 The Hippo pathway contains highly conserved kinases, involving mammalian sterile 20-like kinase 1/2 (MST1/2), large tumor suppressor kinase 1/2 (LATS1/2) and mps one binder 1 (MOB1) A/B, to regulate downstream Yes-associated protein 1 (YAP)/transcriptional coactivator with the PDZ-binding motif, WWTR1 (TAZ). YAP/TAZ could regulate target DNA via directly binding with DNA-binding transcription factors like TEA domain transcription factors (TEAD) and further formation of a complex. When the Hippo pathway is activated, LATS1/2 could phosphorylate YAP/TAZ, hence increasing its degradation and nuclear exclusion by 14-3-3 protein.2,3
Emodin in Rheum undulatum inhibits oxidative stress in the liver via AMPK with Hippo/Yap signalling pathway
Published in Pharmaceutical Biology, 2020
Eun Hye Lee, Su Youn Baek, Ji Young Park, Young Woo Kim
Several of the most strongly induced genes were targets of the AMPK signalling pathway and the Hippo pathway (Figure 6(A); Tables 2 and 3). Prkaa1 (5′-AMP-activated protein kinase catalytic subunit α-1) was significantly upregulated (1.25-fold), while Prkaa2 (5′-AMP-activated protein kinase catalytic subunit α-2) and Prkab1 (5′-AMP-activated protein kinase subunit β-1) were significantly downregulated (0.08-fold: Prkaa2, 0.78-fold: Prkab1) in response to emodin when compared with the control (Figure 6(A); Table 2). The commonly known YAP target genes, Lats1 (Large Tumour Suppressor Kinase 1) and Mob1b (MOB Kinase Activator 1B), showed a striking level of upregulation (1.15-fold: Lats1, 1.36-fold: Mob1b; Figure 6(B); Table 2). However, Ajuba, a negative regulator of the Hippo signalling pathway, was greatly downregulated in response to emodin injection (0.29-fold; Figure 6(B); Table 2). qPCR also confirmed the effect of emodin on the gene expressions. In addition, emodin increased the protein expression of p-AMPKα and p-YAP in the livers of mice as assessed by immunoblot analysis (data not shown). Thus, these data show that emodin triggers the induction of AMPK and Hippo signalling pathways.
Angiotensin-converting enzyme 2 activation suppresses pulmonary vascular remodeling by inducing apoptosis through the Hippo signaling pathway in rats with pulmonary arterial hypertension
Published in Clinical and Experimental Hypertension, 2019
Daole Yan, Gang Li, Yaozhong Zhang, Yinglong Liu
ACE2, its effector angiotensin- (1–7), and receptor Mas comprise a vasoactive axis, which antagonizes the biological effects of angiotensin II in humans. Mas was first isolated from human epidermal cancer cells in 1986 (13), and its amino acid sequence was found to have seven transmembrane domains suggesting that this protein belongs to the G protein-coupled receptor (GPCR) family. One GPCR-regulated pathway, the Hippo pathway, has been reported to play an important role in cell proliferation and apoptosis (14), and consists of mammalian sterile 20-like 1/2 (MST1/2) and large tumor suppressor 1/2 (LATS1/2) (15,16). As a major reciprocal effector of Hippo signaling, Yap regulates other transcriptional factors to promote proliferation and inhibit apoptosis in cells (17). LATS1/2 is activated by MST1/2, which then inhibits Yap activity through phosphorylation (18). GPCRs serve as upstream regulators of Hippo signaling, and activate or inactivate the Hippo pathway via the co-transcription factor Yap. Furthermore, Wennmann et al reported that the Hippo pathway is regulated by angiotensin II and angiotensin II type 1 receptor through the suppression of LATS kinase activity in HEK293T cells (19). Because ACE2 primarily mediates the antagonistic effects of angiotensin II, we hypothesized that the Hippo pathway might participate in the effect of ACE2 activation on pulmonary remodeling by modulating the apoptosis of pulmonary vascular cells.