Synergistic effects of phenylhexyl isothiocyanate and LY294002 on the PI3K/Akt signaling pathway in HL-60 cells

Yang, Hui-Cong; Huang, Yiqun; Zou, Yong; Ma, Xudong

doi:10.3892/ol.2017.6556

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…Moreover, we found that the apoptosis rates of CCA stem cells treated with GATA1 silencing and PI3K/AKT pathway inactivation were significantly increased. A former research demonstrated the association of LY294002 with apoptosis of human nasopharyngeal carcinoma,37 and other studies also revealed that LY294002 is capable of inducing apoptosis in HL-60 cells38 and promoting cell apoptosis caused by melatonin 39. It was also reported that osthole promotes apoptosis while impeding proliferation through the PI3K/AKT pathway in intrahepatic CCA 24.…”

Section: Discussionmentioning

confidence: 91%

<p>GATA1 gene silencing inhibits invasion, proliferation and migration of cholangiocarcinoma stem cells via disrupting the PI3K/AKT pathway</p>

Shi

Zhang²,

et al. 2019

OTT

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Background/aims: Intrahepatic cholangiocarcinoma (CCA) is the second most prevalent type primary liver malignancy, accompanied by an increasing global incidence and mortality rate. Research has documented the contribution of the GATA binding protein-1 (GATA1) in the progression of liver cancer. Here, we aim to investigate the role of GATA1 in CCA stem cells via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Methods: Initially, microarray-based gene expression profiling was employed to identify the differentially expressed genes associated with CCA. Subsequently, an investigation was conducted to explore the potential biological significance behind the silencing of GATA1 and the regulatory mechanism between GATA1 and PI3K/AKT pathway. CCA cell lines QBC-939 and RBE were selected and treated with siRNA against GATA1 or/and a PI3K/AKT pathway inhibitor LY294002. In vivo experiment was also conducted to confirm in vitro findings. Results: GATA1 exhibited higher expression in CCA samples and was predicted to affect the progression of CCA through blockade of the PI3K/AKT pathway. siRNA-mediated downregulation of GATA1 and LY294002 treatment resulted in reduced proliferation, migration and invasion abilities of CCA stem cells, together with impeded tumor growth, and led to increased cell apoptosis and primary cilium expression. Additionally, the siRNA-mediated GATA1 downregulation had an inhibitory effect on the PI3K/AKT pathway. LY294002 was manifested to enhance the inhibitory effects of GATA1 inhibition on CCA progression. These in vitro findings were reproduced in vivo on siRNA against GATA1 or LY294002 injected nude mice. Conclusion: Altogether, the present study highlighted that downregulation of GATA1 via blockade of the PI3K/AKT pathway could inhibit the CCA stem cell proliferation, migration and invasion, and tumor growth, and promote cell apoptosis, primary cilium expression.

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Section: Discussionmentioning

confidence: 91%

<p>GATA1 gene silencing inhibits invasion, proliferation and migration of cholangiocarcinoma stem cells via disrupting the PI3K/AKT pathway</p>

Shi

Zhang²,

et al. 2019

OTT

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“…AKT can also play a significant role in the differentiation of some Yang, Huang, Zou, and Ma (2017) Note. HAT: histone acetyltransferase; HSCs: hematopoietic stem cells.…”

Section: The Importance Of Akt and Its Role In Erythropoiesismentioning

confidence: 99%

PI3k/AKT signaling pathway: Erythropoiesis and beyond

Jafari

Ghadami

Dadkhah

et al. 2018

Journal Cellular Physiology

246

142

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Erythropoiesis is a multi-step process that involves the differentiation of hematopoietic stem cells into mature red blood cells (RBCs). This process is regulated by several signaling pathways, transcription factors and microRNAs (miRNAs). Many studies have shown that dysregulation of this process can lead to hematologic disorders. PI3K/AKT is one of the most important pathways that control many cellular processes including, cell division, autophagy, survival, and differentiation. In this review, we focus on the role of PI3K/AKT pathway in erythropoiesis and discuss the function of some of the most important genes, transcription factors, and miRNAs that regulate different stages of erythropoiesis which play roles in differentiation and maturation of RBCs, prevention of apoptosis, and autophagy induction. Understanding the role of the PI3K pathway in erythropoiesis may provide new insights into diagnosing erythrocyte disorders.

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“…Our data showed that leonurine exhibited significant inhibitory effects on the phosphorylation of PI3K and Akt in HL-60 and U-937 cells. Previous reports (Lu et al 2015;Yang et al 2017) have proven the relationship of the PI3K/ Akt pathway with apoptosis. The PI3K inhibitor LY294002 has been proven to inhibit HL-60 proliferation and induce cell apoptosis.…”

mentioning

confidence: 95%

Anti-leukaemia effects of leonurine in vitro and in vivo

Zhuang

Ruan²,

Jin³

et al. 2021

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The present study was conducted to explore the anti-acute myeloid leukaemia (AML) effects of leonurine. HL-60 and U-937 cells were used to assess the antileukaemia effect of leonurine in vitro, and HL-60 and U-937 xenograft nude mice were used to evaluate its antitumour effect in vivo. Leonurine inhibited the proliferation of HL-60 and U-937 cells in a time-and dose-dependent manner. Moreover, leonurine therapy prevented the growth of tumours in both xenograft animal models. Leonurine could induce apoptosis in HL-60 and U-937 cells. The cytotoxic effects of leonurine on HL-60 and U-937 cells were associated with an increased ratio of Bax/Bcl-2, activation of caspase-3, caspase-8 and caspase-9, and increased expression of cytochrome c in the cytoplasm. Leonurine inhibited activation of the PI3K/Akt pathway in HL-60 and U-937 cells by lowering the phosphorylation levels of PI3K and Akt. Our results indicate that leonurine is a potential anti-AML agent, and this activity may be associated with its repression of the phosphorylation of PI3K and Akt.

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Synergistic effects of phenylhexyl isothiocyanate and LY294002 on the PI3K/Akt signaling pathway in HL-60 cells

Cited by 5 publications

References 40 publications

<p>GATA1 gene silencing inhibits invasion, proliferation and migration of cholangiocarcinoma stem cells via disrupting the PI3K/AKT pathway</p>

<p>GATA1 gene silencing inhibits invasion, proliferation and migration of cholangiocarcinoma stem cells via disrupting the PI3K/AKT pathway</p>

PI3k/AKT signaling pathway: Erythropoiesis and beyond

Anti-leukaemia effects of leonurine in vitro and in vivo

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