Over-expressed human TREK-1 inhibits CHO cell proliferation via inhibiting PKA and p38 MAPK pathways and subsequently inducing G1 arrest

Zhang, Man; Yin, Huajing; Wang, Weiping; Jiang, Li; Wang, Xiaoliang

doi:10.1038/aps.2016.65

Cited by 12 publications

(12 citation statements)

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“…Previous studies have shown the close correlation between the pathological process of ischemic stroke and the levels of TREK-1 mRNA and protein expressions [31, 32]. Although the mechanism by which TREK-1 expression affects cellular functions remains unclear, it is believed, under hypoxic conditions, that the upregulation of TREK-1 expression inhibits the activity of protein kinase A and the expression of cyclin D1 [33] and decreases neuronal stem cell [34], astrocyte [35], and human osteoblasts proliferation [35, 36]. Recently, it has been demonstrated that l-NBP promotes neurogenesis and tissue recovery through inhibition of TREK-1 channels [37].…”

Section: Nbp and Ischemic Strokementioning

confidence: 99%

A Review of Recent Advances in Neuroprotective Potential of 3-N-Butylphthalide and Its Derivatives

Abdoulaye

Guo

2016

BioMed Research International

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The research of alternative treatment for ischemic stroke and degenerative diseases has always been a priority in neurology. 3-N-Butylphthalide (NBP), a family of compounds initially isolated from the seeds of Apium graveolens Linn., has shown significant neuroprotective effects. Previous extensive studies have demonstrated that NBP promotes a better poststroke outcome and exerts a multitargeted action on several mechanisms, from oxidative stress to mitochondrial dysfunction to apoptosis to inflammation. Additionally, recent findings on several neurological disorders have shown that NBP's beneficial effects extend beyond the management of stroke. However, despite the increasing number of studies toward a better understanding and the rapid advances made in therapeutic options, to date, dl-3-N-butylphthalide, a synthetic variation of l-3-N-butylphthalide, remains the only clinically approved anti-ischemic agent in China, stressing the difficulties for a viable and effective transition from experimental to clinical practice. Events indicate that NBP, due to its multitargeted effect and the adaptability of its basic structure, can be an important game changer and a precursor to a whole new therapeutic approach to several neurological conditions. The present review discusses recent advances pertaining to the neuroprotective mechanisms of NBP-derived compounds and the possibility of their clinical implementation in the management of various neurological conditions.

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Section: Nbp and Ischemic Strokementioning

confidence: 99%

A Review of Recent Advances in Neuroprotective Potential of 3-N-Butylphthalide and Its Derivatives

Abdoulaye

Guo

2016

BioMed Research International

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“…We focused our attention in a novelty promising target such as the voltage‐gated potassium channels, K V , which are present in tumor cells, and they play important roles in the regulation of tumor cell proliferation, cell cycle progression, migration, and apoptosis (Chittajallu et al., ; Comes et al., ; Fukushiro‐Lopes et al., ; Han et al., ; Lang et al., ; Ouadid‐Ahidouch & Ahidouch, ; Pardo, ; Pardo et al., ; Sauter et al., ; Stuhmer et al., ; Wang, ; Wonderlin et al., ; Zhang et al., ). The modulation of potassium channels has been identified as target for some 4‐substituted quinolines and 4‐substituted quinolin‐2‐ones (Dinsmore & Bergman, ; Galanakis et al., ; Hewawasam et al., , ; Kang et al., ; Wulff et al., ).…”

Section: Resultsmentioning

confidence: 99%

“…SKBr3 cancer cell was used to perform this assay. It is well documented that several voltage‐gated K+ channels of the Shaker family (K V ) are present in breast cancer tissue or cell lines (Fukushiro‐Lopes et al., ; Han et al., ; Sauter et al., ; Stuhmer et al., ; Zhang et al., ). Results are shown in Figure .…”

Section: Resultsmentioning

confidence: 99%

“…K+ currents play an important role in multiple cellular functions such as the maintenance of resting membrane potential and the active repolarization of the action potential, the regulation of cell volume, differentiation, proliferation, cell cycle progression, migration, and apoptosis (Comes et al, 2015). Various types of voltage-gated K+ channels, K V , are present in tumor cells, and the potassium channel functions can regulate through both mechanisms: canonical ion permeation-dependent or non-canonical ion permeation-dependent (Chittajallu et al, 2002;Fukushiro-Lopes et al, 2018;Han et al, 2008;Lang et al, 2005;Ouadid-Ahidouch & Ahidouch, 2008;Pardo, 2004;Pardo, Contreras-Jurado, Zientkowska, Alves, & Stuhmer, 2005;Sauter, Sørensen, Rapedius, Brüggemann, & Novak, 2006;Stuhmer, Alves, Hartung, Zientkowska, & Pardo, 2006;Wang, 2004;Wonderlin, Woodfork, & Strobl, 1995;Zhang, Yin, Wang, Li, & Wang, 2016). Specifically, Kv1.3 and Kv1.5 are widely implicated in the development of different tumors (Comes et al, 2015;Dinsmore & Bergman, 2003;Fukushiro-Lopes et al, 2018;Galanakis et al, 1995;Han et al, 2008;Hewawasam et al, 1997Hewawasam et al, , 2003Kang et al, 2005;Sauter et al, 2006;Stuhmer et al, 2006;Wulff, Castle, & Pardo, 2009;Zhang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Various types of voltage-gated K+ channels, K V , are present in tumor cells, and the potassium channel functions can regulate through both mechanisms: canonical ion permeation-dependent or non-canonical ion permeation-dependent (Chittajallu et al, 2002;Fukushiro-Lopes et al, 2018;Han et al, 2008;Lang et al, 2005;Ouadid-Ahidouch & Ahidouch, 2008;Pardo, 2004;Pardo, Contreras-Jurado, Zientkowska, Alves, & Stuhmer, 2005;Sauter, Sørensen, Rapedius, Brüggemann, & Novak, 2006;Stuhmer, Alves, Hartung, Zientkowska, & Pardo, 2006;Wang, 2004;Wonderlin, Woodfork, & Strobl, 1995;Zhang, Yin, Wang, Li, & Wang, 2016). Specifically, Kv1.3 and Kv1.5 are widely implicated in the development of different tumors (Comes et al, 2015;Dinsmore & Bergman, 2003;Fukushiro-Lopes et al, 2018;Galanakis et al, 1995;Han et al, 2008;Hewawasam et al, 1997Hewawasam et al, , 2003Kang et al, 2005;Sauter et al, 2006;Stuhmer et al, 2006;Wulff, Castle, & Pardo, 2009;Zhang et al, 2016). Experimental evidences have demonstrated that pharmacological activation of K+ channels induces a hyperpolarization of plasma membrane, leading to cell proliferation inhibition in different cancer cells (Fukushiro-Lopes et al, 2018;Han et al, 2008;Sauter et al, 2006;Stuhmer et al, 2006;Zhang et al, 2016), representing a potential target for the design of new anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

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Identification of dehydroxy isoquine and isotebuquine as promising anticancer agents targeting K+ channel

et al. 2019

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Traditional antimalarial drugs based on 4‐aminoquinolines have exhibited good antiproliferative activities against human tumor cells; however, their low relative efficacy has limited their corresponding clinical uses. In order to identify new potent anticancer agents based on 4‐aminoquinoline, we evaluated the antiproliferative activity of a series of dehydroxy isoquines and isotebuquines against five human cancer lines. HeLa and SKBr3 were significantly more sensitive to the action of tested quinolines than the A549, MCF‐7, and PC‐3 cancer lines. Compound 2h was by far the most potent derivative against four of the tested lines (except to PC3 line), exhibiting low micromolar or nanomolar IC50 values superior to adriamycin reference, low toxicities on dermis human fibroblasts (LD50 > 250 μM), and excellent selectivity indexes against the mentioned cancer cells. A structure–activity relationship analysis put in evidence that a pyrrolidine or morpholine moiety as N‐alkyl terminal substitution and the incorporation of the extra phenyl attached to aniline ring are pharmacophore essentials for improvement the anticancer activity of the studied dehydroxy isoquines and isotebuquines. From the results, compound 2h emerged as a promising anticancer candidate for further in vitro assays against resistant‐strain and in vivo studies as well as pharmacokinetic and genotoxicity studies. Mechanistic assays suggested that the most active quinoline 2h act as calcium‐activated potassium channel activator.

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Electron Spin Polarization Engineering in Ferromagnetic Bioheterojunction for Sonotherapy of Osteomyelitis

Ding,

Li,

Liu

et al. 2024

Adv Funct Materials

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Electron spinning polarization has garnered increased attention for its potential to enhance device properties. However, its application in life health, specifically in anti‐infection and tissue repair, remains under‐explored. In this study, a ferromagnetic heterojunction CF (Fe3O4/TiO2) is constructed with spin‐polarized electrons, demonstrating efficient antibiosis performance with ultrasound (US) assistance. The antibacterial mechanism is elucidated as follows: spin‐polarized metallic states of Fe3O4 induce an asymmetric distribution in the electron spin state of TiO2, increasing the density of states of spin‐polarized electrons near the Fermi level of CF. Under US treatment, the built‐in electric field and spin‐polarized electrons in CF synergistically suppress the recombination of sono‐activated carriers, promoting reactive oxygen species (ROS) production. Simultaneously, the bacterial membrane is influenced by the micromagnetic field induced by spin‐polarized electrons, causing a severe disturbance in the bacterial respiratory chain. The combined damage from ROS and disturbed respiratory chain results in bacterial death. Fortunately, the micromagnetic field built by CF activates specific mechanosensitive ion channels, including TREK1, Piezo1, and related pathways, enhancing osteoblast differentiation. Sonotherapy using CF exhibits an excellent therapeutic effect in treating osteomyelitis. This study provides novel insights into manipulating spin electrons for applications in life health.

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Over-expressed human TREK-1 inhibits CHO cell proliferation via inhibiting PKA and p38 MAPK pathways and subsequently inducing G1 arrest

Abstract: TREK-1 overexpression suppresses CHO cell proliferation by inhibiting the activity of PKA and p38/MAPK signaling pathways and subsequently inducing G1 phase cell arrest.

Cited by 12 publications

References 40 publications

A Review of Recent Advances in Neuroprotective Potential of 3-N-Butylphthalide and Its Derivatives

A Review of Recent Advances in Neuroprotective Potential of 3-N-Butylphthalide and Its Derivatives

Identification of dehydroxy isoquine and isotebuquine as promising anticancer agents targeting K+ channel

Electron Spin Polarization Engineering in Ferromagnetic Bioheterojunction for Sonotherapy of Osteomyelitis

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