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doi:10.1038/sj/leu/2401415

Cited by 34 publications

(18 citation statements)

References 8 publications

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“…Constitutively active STAT3 plays critical roles in the induction of resistance to apoptosis,9 probably by increasing the expression of cyclin D1 and Bcl-2 32,33. AA-PMe-induced suppression of cell proliferation and cell cycle arrest at the G0/G1 phase were closely associated with the downregulation of cyclin D1 expression, which was consistent with the requirement of cyclin D1 for cell cycle transition from G1 to S phase.…”

Section: Discussionsupporting

confidence: 70%

A novel synthetic Asiatic acid derivative induces apoptosis and inhibits proliferation and mobility of gastric cancer cells by suppressing STAT3 signaling pathway

Wang¹,

Yue

Cao³

et al. 2016

OTT

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Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA) derivative, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells. This inhibition was mediated by blockade of Janus-activated kinase 2. Additionally, AA-PMe regulated the expression of STAT3-modulated gene products, including cyclin D1, Bax, Bcl-2, c-Myc, and matrix metalloproteinase (MMP)-2 and MMP-9. Finally, transfection with both a STAT3 mimic and an inhibitor reversed the AA-PMe-driven modulation of STAT3 downstream gene products. Overall, these results suggest that AA-PMe is a novel blocker of STAT3 activation and has the potential for the prevention and treatment of gastric cancer.

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Section: Discussionsupporting

confidence: 70%

A novel synthetic Asiatic acid derivative induces apoptosis and inhibits proliferation and mobility of gastric cancer cells by suppressing STAT3 signaling pathway

Wang¹,

Yue

Cao³

et al. 2016

OTT

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“…Previous studies have confirmed that STAT3 alterations affect Bcl-2 and Bax protein expression (decreased Bcl-2 and increased Bax) and induce inflammation and apoptosis in many types of tumor cells (66–68). Lee et al (69) demonstrated that co-activated NF-κB and STAT3 modulate Bax/Bcl-xL expression and promote cell survival in head and neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 79%

“…In mycosis fungoides tumor cells, some apoptosis-related genes, such as Bcl-2 and Bax, have been identified as STAT3 target genes (66). In primary cortical neurons and murine models of stroke, the activation of the Jak2/Stat3 pathway by secretoneurin has been found to exert neuroprotective effects and induce neuronal plasticity after hypoxia and ischemic insult (70).…”

Section: Discussionmentioning

confidence: 99%

Non-invasive remote limb ischemic postconditioning protects rats against focal cerebral ischemia by upregulating STAT3 and reducing apoptosis

Cheng

et al. 2014

International Journal of Molecular Medicine

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The signal transducer and activator of transcription 3 (STAT3) signaling pathway has been implicated in cell apoptosis and inflammatory processes. Ischemic preconditioning (IPC) and ischemic postconditioning (IPTC) inhibit both of these processes. In the present study, we investigated the role of phosphorylated STAT3 (p-STAT3)-mediated apoptosis and inflammation following non-invasive remote limb IPTC (NRIPoC) using a classic rat model of focal cerebral ischemia. Forty-five adult male Sprague-Dawley rats were divided randomly into 3 groups (n=15 per group): the sham-operated, ischemia/reperfusion (I/R) and NRIPoC groups. NRIPoC was implemented at the beginning of reperfusion. At 24 h after cerebral reperfusion, we evaluated the neurological deficit score (NDS), assessed the cerebral infarct size and tissue morphology, and evaluated neuronal apoptosis. The protein expression levels of Bcl-2, Bax, nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α) and p-STAT3 in the penumbra region were assessed by western blot analysis. The cerebral infarct volume, the number of apoptotic cells and the protein expression levels of Bcl-2, Bax, NF-κB and TNF-α were all found to be increased in the I/R group compared with the sham-operated group. However, these levels were decreased in the NRIPoC group compared with the I/R group. The number of apoptotic cells in the penumbra in the I/R group was increased compared with that in the NRIPoC and sham-operated groups. The protein expression of p-STAT3 was increased in the NRIPoC group compared with the sham-operated and I/R groups. These results indicate that the protective effects of NRIPoC against cerebral I/R injury may be related to the attenuation of neuronal apoptosis and inflammation through the activation of STAT3.

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“…Constitutive STAT3 activation has been known to induce resistance to apoptosis [48], possibly through up-regulation of Bcl-2, Bcl-xl, IAP1/2, and Survivin expression [49]. The down-regulation of Cyclin D1 expression by BSN associated with the suppression in proliferation and accumulation of cells in the sub-G1 phase of the cell cycle, suggesting that Cyclin D1 plays an important role in the observed anti-proliferative effect of BSN.…”

Section: Discussionmentioning

confidence: 99%

Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel

et al. 2015

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Persistent phosphorylation of signal transducers and activators of transcription 3 (STAT3) is frequently observed in tumor cells. We found that brassinin (BSN) suppressed both constitutive and IL-6-inducible STAT3 activation in lung cancer cells. Moreover, BSN induced PIAS-3 protein and mRNA, whereas the expression of SOCS-3 was reduced. Knockdown of PIAS-3 by small interfering RNA prevented inhibition of STAT3 and cytotoxicity by BSN. Overexpression of SOCS-3 in BSN-treated cells increased STAT3 phosphorylation and cell viability. BSN down-regulated STAT3-regulated gene products, inhibited proliferation, invasion, as well as induced apoptosis. Most importantly, when administered intraperitoneally, combination of BSN and paclitaxel significantly decreased the tumor development in a xenograft lung cancer mouse model associated with down-modulation of phospho-STAT3, Ki-67 and CD31. We suggest that BSN inhibits STAT3 signaling through modulation of PIAS-3 and SOCS-3, thereby attenuating tumor growth and increasing sensitivity to paclitaxel.

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Cited by 34 publications

References 8 publications

A novel synthetic Asiatic acid derivative induces apoptosis and inhibits proliferation and mobility of gastric cancer cells by suppressing STAT3 signaling pathway

A novel synthetic Asiatic acid derivative induces apoptosis and inhibits proliferation and mobility of gastric cancer cells by suppressing STAT3 signaling pathway

Non-invasive remote limb ischemic postconditioning protects rats against focal cerebral ischemia by upregulating STAT3 and reducing apoptosis

Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel

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