Dehydrocostus Lactone Suppresses Proliferation of Human Chronic Myeloid Leukemia Cells Through Bcr/Abl‐JAK/STAT Signaling Pathways

Cai, Hong; Qin, Xiaosong; Yang, Chunhui

doi:10.1002/jcb.25994

Cited by 34 publications

(28 citation statements)

References 26 publications

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“…The study from Li Lin et al has shown that the STAT3 inhibitor FLLL32 inhibits the expression of CCND1, which is one of the STAT3 downstream targets in cancer cells. 33 Previous studies have revealed that JAK2 mediates the increase in c-Myc expression in CML cells, 34 while the increase expression of Bcl-xL is associated with activation of JAK2 and STAT3 23 . Consistent with our data, Ma Lingdi and co-workers have found that inactivation of JAK2/STAT3 and down-regulation of c-Myc and CCND1 induced cell cycle arrest in K562 cells.…”

Section: Discussionmentioning

confidence: 99%

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Deletion of MBD2 inhibits proliferation of chronic myeloid leukaemia blast phase cells

Cheng

Tang

Chen

et al. 2018

Cancer Biology & Therapy

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Aberrant methylation of tumour suppressor genes is associated with the progression to a blast crisis in chronic myeloid leukaemia (CML). Methyl-CpG-binding domain protein 2 (MBD2) has been studied as a "reader" of DNA methylation in many cancers, but its role in CML is unclear. We constructed cell models of a homozygous deletion mutation of MBD2 using gene-editing technology in K562 cells and BV173 cells. Here, we demonstrated that the deletion of MBD2 inhibited cell proliferation capacity in vitro. MBD2 deletion also significantly inhibited K562 cell proliferation in a xenograft tumour model in vivo. Additionally, the JAK2/STAT3 signalling pathway, which is abnormally active in CML, was inhibited by MBD2 deletion, and MBD2 deletion could up-regulate the expression of SHP1. In conclusion, our findings suggest that MBD2 is a candidate therapeutic strategy for the CML blast phase.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, the expressions of myeloid differentiation markers (CD11b, CD11c and CD14) were detected by flow cytometry. [21][22][23] Only the level of CD11b and CD14 were slightly higher in KO cells than in WT cells, but these changes were not statistically significant (Supplement Fig. 1D).…”

Section: Deletion Of Mbd2 Inhibits the Proliferation Of K562 Cells Inmentioning

confidence: 92%

Deletion of MBD2 inhibits proliferation of chronic myeloid leukaemia blast phase cells

Cheng

Tang

Chen

et al. 2018

Cancer Biology & Therapy

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“…Bortezomib can induce apoptosis of K562 leukemic cells by interacting with JAK/STAT pathway (29). JAK/STAT signaling pathway is found to mediate sehydrocostus lactone-suppressed proliferation of CML cells (30). In this study, overexpression of miR-574-3p could inhibit the activation of JAK/STAT3 pathway, which was rescued by overexpression of IL6.…”

Section: Discussionmentioning

confidence: 54%

Overexpression of miR‑574‑3p suppresses proliferation and induces apoptosis of chronic myeloid leukemia cells via targeting IL6/JAK/STAT3 pathway

Yang

Zhang

et al. 2018

Exp Ther Med

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The present study aimed to elucidate the potential roles and regulatory mechanism of microRNA (miR)-574-3p in the development of chronic myeloid leukemia (CML). The expression of miR-574-3p in peripheral blood obtained from patients with CML was examined. Subsequently, miR-574-3p was overexpressed and suppressed in CML K562 cells to further investigate the effects of miR-574-3p on cell proliferation, and apoptosis. Furthermore, a luciferase reporter assay was performed to investigate whether interleukin-6 (IL-6) was a target of miR-574-3p. In addition, the regulatory association between miR-574-3p and the IL-6/Janus kinase (JNK)/signal transducer and activator of transcription-3 (STAT3) signaling pathway was explored. The expression of miR-574-3p in the peripheral blood obtained from patients with CML was significantly lower compared with that in healthy controls. Overexpression of miR-574-3p significantly inhibited the proliferation and induced the apoptosis of K562 cells, whereas suppression of miR-574-3p exhibited opposite effects. In addition, IL-6 was identified to be a direct target of miR-574-3p. Overexpression of IL-6 significantly promoted the proliferation and inhibited the apoptosis of K562 cells. Furthermore, overexpression of miR-574-3p inhibited the activation of the JAK/STAT3 signaling pathway, which was rescued by overexpression of IL-6. The results of the current study indicate that miR-574-3p overexpression may serve an important role in inhibiting proliferation and inducing apoptosis of K562 cells via suppression of IL-6/JAK/STAT3 signaling pathway activation. miR-574-3p may serve as a potential therapeutic target for CML.

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“…Previous studies demonstrated that Stat5 is the major downstream target of Bcr/Abl and that inhibition of Bcr/Abl could significantly downregulate the levels of Stat5 (Berger et al, ). In addition, Bcr/Abl/Stat5 inhibition induced apoptosis in CML cells by suppressing Stat5‐dependent transcriptional regulation of Bcl‐2 family members such as Mcl‐1, Bcl‐2, and Bcl‐xL (Cai, Qin, & Yang, ; Wang et al, ). Therefore, targeting Bcr/Abl tyrosine activity and Stat proteins to induce cell apoptosis and reduce proliferation is a promising approach for anti‐CML drug development.…”

Section: Introductionmentioning

confidence: 99%

Costunolide promotes imatinib‐induced apoptosis in chronic myeloid leukemia cells via the Bcr/Abl–Stat5 pathway

Cai

Yang

2018

Phytotherapy Research

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Costunolide, a sesquiterpene lactone, is a small molecular monomer extracted from Inula helenium (Compositae). In the present study, we assessed the antileukemia effects of costunolide on the human chronic myeloid leukemia cell line K562 and its combined activity with imatinib. A Cell Counting Kit-8 assay demonstrated that costunolide significantly inhibited K562 cell proliferation and enhanced imatinib-induced anti-proliferative activity. We found that costunolide significantly induced mitochondrial apoptosis in K562 cells by modulating the protein levels of Bcl-2 family members and by inducing caspase activation. Costunolide promoted imatinib-induced apoptosis via the Bcr/Abl-signal transducer and activator of transcription 5 pathway. Costunolide inhibited proliferation by inducing cell cycle arrest in the G /M phase by decreasing cyclin B1 and cyclin-dependent kinase 2 expression and increasing p21 expression. Together, these results demonstrate that costunolide may be a potent therapeutic agent against chronic myeloid leukemia.

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Dehydrocostus Lactone Suppresses Proliferation of Human Chronic Myeloid Leukemia Cells Through Bcr/Abl‐JAK/STAT Signaling Pathways

Cited by 34 publications

References 26 publications

Deletion of MBD2 inhibits proliferation of chronic myeloid leukaemia blast phase cells

Deletion of MBD2 inhibits proliferation of chronic myeloid leukaemia blast phase cells

Overexpression of miR‑574‑3p suppresses proliferation and induces apoptosis of chronic myeloid leukemia cells via targeting IL6/JAK/STAT3 pathway

Costunolide promotes imatinib‐induced apoptosis in chronic myeloid leukemia cells via the Bcr/Abl–Stat5 pathway

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