Honokiol Inhibits Constitutive and Inducible STAT3 Signaling via PU.1-Induced SHP1 Expression in Acute Myeloid Leukemia Cells

Bi, Lei; Yu, Zhijie; Wu, Jianbo; Kang, Yu; Hong, Guangliang; Lu, Zhongqiu; Gao, Shenmeng

doi:10.1620/tjem.237.163

Cited by 23 publications

(22 citation statements)

References 30 publications

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“…Similarly, honokiol also induces apoptosis through the suppression of JAK2/STAT3, Akt and Erk signalling pathways in human oral squamous cell carcinoma (SAS and OCEM-1) cell lines [95]. Similar effect was observed in oral cancer cells where honokiol suppressed JAK2/STAT3 activation and, inhibited IL-6-mediated cell migration [95,183]. Furthermore, another study indicated that honokiol induces apoptosis in human glioblastoma cell line U87 through suppressing the phosphorylation of STAT3 (Tyr705), down-regulating survivin, and upregulating cleaved caspase-3 expression [98].…”

Section: Signal Transducers and Activators Of Transcription (Stats)mentioning

confidence: 75%

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Honokiol: A Review of Its Anticancer Potential and Mechanisms

Ong

Lee

Tang

et al. 2019

Cancers

131

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Cancer is characterised by uncontrolled cell division and abnormal cell growth, which is largely caused by a variety of gene mutations. There are continuous efforts being made to develop effective cancer treatments as resistance to current anticancer drugs has been on the rise. Natural products represent a promising source in the search for anticancer treatments as they possess unique chemical structures and combinations of compounds that may be effective against cancer with a minimal toxicity profile or few side effects compared to standard anticancer therapy. Extensive research on natural products has shown that bioactive natural compounds target multiple cellular processes and pathways involved in cancer progression. In this review, we discuss honokiol, a plant bioactive compound that originates mainly from the Magnolia species. Various studies have proven that honokiol exerts broad-range anticancer activity in vitro and in vivo by regulating numerous signalling pathways. These include induction of G0/G1 and G2/M cell cycle arrest (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins), epithelial-mesenchymal transition inhibition via the downregulation of mesenchymal markers and upregulation of epithelial markers. Additionally, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases (activation of 5 AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling), inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)). Combining these studies provides significant insights for the potential of honokiol to be a promising candidate natural compound for chemoprevention and treatment.

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Section: Signal Transducers and Activators Of Transcription (Stats)mentioning

confidence: 75%

“…In summary, both microneedles and chemical enhancers can improve the absorption of honokiol through the skin. Directly applying honokiol on mammary papilla is a potential administration route which can increase localized delivery into breast tissue [183].…”

Section: Metabolism Bioavailability and Pharmacological Relevance Omentioning

confidence: 99%

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Ong

Lee

Tang

et al. 2019

Cancers

131

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“…AML is a kind of hematological malignancies characterized by the infiltration of blasts to the bone marrow, blood, and other tissues. 19,30 Constitutive activation of STAT3 has a critical impact on the carcinogenesis, 15 principle of turmeric) as a phytochemical inhibits proliferation in different types of cancer cells via targeting multiple cellular signaling pathways such as NF-kB, the mitogen-activated protein kinase, Wnt, PI3K/AKT/mTOR and Notch-mediated signaling pathways. 31,32 During the last few years, several studies have investigated the potential impact of CUR (alone or in combination with other anticancer agents) on cancer stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…12,13 Inhibition of STAT3 signaling cascades causes cell apoptosis and ultimately leukemia remission. 14,15 BCL-XL is a member of BCL-2 families. 16 BCL-XL has an anti-apoptotic effect, controlled by several mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Combined with Thalidomide Reduces Expression of STAT3 and Bcl-xL, Leading to Apoptosis in Acute Myeloid Leukemia Cell Lines

Kian¹,

Salemi²,

Bahadoran³

et al. 2020

DDDT

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Introduction: Acute myeloid leukemia (AML) is a type of blood disorder that exhibits uncontrolled growth and reduced ability to undergo apoptosis. Signal transducer and activator of transcription 3 (STAT3) is a family member of transcription factors which promotes carcinogenesis in most human cancers. This effect on AML is accomplished through deregulation of several critical genes, such as B cell lymphoma-extra-large (BCL-XL) which is anti-apoptotic protein. The aim of this study was to evaluate the effect of curcumin (CUR) and thalidomide (THAL) on apoptosis induction and also the alteration of the mRNA expression level of STAT3 and BCL-XL mRNA on AML cell line compounds. Methods: The growth inhibitory effects of CUR and THAL and their combination were measured by MTT assay in U937 and KG-1 cell lines. The rates of apoptosis induction and cell cycle analysis were measured by concurrent staining with Annexin V and PI. The mRNA expression level of STAT3 and BCL-XL was evaluated by Real-Time PCR. Results: CUR inhibited proliferation and induced apoptosis in both KG-1 and U937 cells and this effect increased by combination with THAL. The expression level of STAT3 and BCL-XL was significantly down-regulated in KG-1 cells after treatment by CUR and THAL and their combination. Conclusion: Overall, our findings suggested that down-regulation of STAT3 and BCL-XL mRNA expression in response to CUR and THAL treatment lead to inhibition of cell growth and induction of apoptosis.

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“…Constitutive and inducible activation of STAT3 signaling promotes carcinogenesis in many human cancers such as acute myeloid leukemia. Negative regulators, such as protein tyrosine phosphatase SHP-1, may suppress the activated STAT3 signaling [20]. Additionally, 3 phosphatases, TC45, SHP-1 and SHP-2, are the primary contributory enzymes of UVB-mediated STAT3 dephosphorylation, and this may be a protective mechanism against UV skin carcinogenesis [21].…”

Section: Discussionmentioning

confidence: 99%

Verbascoside Inhibits Glioblastoma Cell Proliferation, Migration and Invasion While Promoting Apoptosis Through Upregulation of Protein Tyrosine Phosphatase SHP-1 and Inhibition of STAT3 Phosphorylation

Jia

Wang

Zou

et al. 2018

Cell Physiol Biochem

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Background/Aims: As a natural antioxidant, verbascoside (VB) is proved to be a promising method for the treatment of oxidative-stress-related neurodegenerative diseases. Thus, this study aimed to investigate the effects of VB on glioblastoma cell proliferation, apoptosis, migration, and invasion as well as the mechanism involving signal transducer and activator of transcription 3 (STAT3) and Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). Methods: U87 cells were assigned to different treatments. The MTT assay was used to test cell proliferation, flow cytometry was used to detect cell apoptosis, and a Transwell assay was used for cell migration and invasion. We analyzed the glioblastoma tumor growth in a xenograft mouse model. Western blot analysis was employed to determine the protein expression of related genes. Results: Glioblastoma cells exhibited decreased cell proliferation, migration, invasion, and increased apoptosis when treated with VB or TMZ. Western blot analysis revealed elevated SHP-1 expression and reduced phosphorylated (p)-STAT3 expression in glioblastoma cells treated with VB compared with controls. Correspondingly, in a xenograft mouse model treated with VB, glioblastoma tumor volume and growth were decreased. Glioblastoma xenograft tumors treated with VB showed elevated SHP-1, Bax, cleaved caspase-3, and cleaved PARP expression and reduced p-STAT3, Bcl-2, survivin, MMP-2, and MMP-9 expression. siRNA-SHP-1 inhibited the VB effects on glioblastoma. Conclusion: This study demonstrates that VB inhibits glioblastoma cell proliferation, migration, and invasion while promoting apoptosis via SHP-1 activation and inhibition of STAT3 phosphorylation.

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Honokiol Inhibits Constitutive and Inducible STAT3 Signaling via PU.1-Induced SHP1 Expression in Acute Myeloid Leukemia Cells

Cited by 23 publications

References 30 publications

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Honokiol: A Review of Its Anticancer Potential and Mechanisms

<p>Curcumin Combined with Thalidomide Reduces Expression of <em>STAT3</em> and <em>Bcl-xL</em>, Leading to Apoptosis in Acute Myeloid Leukemia Cell Lines</p>

Verbascoside Inhibits Glioblastoma Cell Proliferation, Migration and Invasion While Promoting Apoptosis Through Upregulation of Protein Tyrosine Phosphatase SHP-1 and Inhibition of STAT3 Phosphorylation

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