Homoharringtonine suppresses imatinib resistance via the Bcl-6/p53 pathway in chronic myeloid leukemia cell lines

Wang, Qian; Ding, Wei; Ding, Yihan; Ma, Jingjing; Qian, Zhiguo; Shao, Jing-xian; Li, Yufeng

doi:10.18632/oncotarget.16731

Cited by 13 publications

(7 citation statements)

References 33 publications

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“…Therefore, it is particularly important to identify new lung cancer targets and targeted drugs. A combination of HHT and VCR has been proven to be effective; imatinib has a good therapeutic effect on leukemia [37,38]. As the target of HHT was different from that of other lung cancer drugs, it can be expected that the combination of HHT and other lung cancer drugs will produce enhanced therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

TMEM16A, a Homoharringtonine Receptor, as a Potential Endogenic Target for Lung Cancer Treatment

Guo

Bai

Shi

et al. 2021

IJMS

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Lung cancer has the highest rate of incidence and mortality among all cancers. Most chemotherapeutic drugs used to treat lung cancer cause serious side effects and are susceptible to drug resistance. Therefore, exploring novel therapeutic targets for lung cancer is important. In this study, we evaluated the potential of TMEM16A as a drug target for lung cancer. Homoharringtonine (HHT) was identified as a novel natural product inhibitor of TMEM16A. Patch-clamp experiments showed that HHT inhibited TMEM16A activity in a concentration-dependent manner. HHT significantly inhibited the proliferation and migration of lung cancer cells with high TMEM16A expression but did not affect the growth of normal lung cells in the absence of TMEM16A expression. In vivo experiments showed that HHT inhibited the growth of lung tumors in mice and did not reduce their body weight. Finally, the molecular mechanism through which HHT inhibits lung cancer was explored by western blotting. The findings showed that HHT has the potential to regulate TMEM16A activity both in vitro and in vivo and could be a new lead compound for the development of anti-lung-cancer drugs.

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Section: Discussionmentioning

confidence: 99%

TMEM16A, a Homoharringtonine Receptor, as a Potential Endogenic Target for Lung Cancer Treatment

Guo

Bai

Shi

et al. 2021

IJMS

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“…In chronic myelogenous leukemia (K562), homoharringtonine increases the activity of imatinib by downregulating ZFX mRNA, blocking the bcl-6/p53 pathway, and inducing apoptosis (Q. Wang et al, 2017b ). In addition to the apoptotic pathway, homoharringtonine has been demonstrated to induce autophagy in imatinib-resistant K562G cells through degradation of the BCR-ABL protein mediated by p62 and silencing of the main autophagic proteins Beclin-1 and ATG5 ( Figure 11 ) (S. Li et al, 2020b ).…”

Section: Anticancer Plant-based Alkaloids: Clinical Trialsmentioning

confidence: 99%

“…Based on previous intense preclinical research and clinical trials, homoharringtonine has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with chronic myeloid lymphoma and chronic myeloid leukemia resistance to imatinib and/or other tyrosine kinase inhibitors (Q. Wang et al, 2017b ). Recently, it has been reported to be effective in patients with myelodysplastic syndrome in clinical phase II ( Daver et al, 2013 ).…”

Section: Anticancer Plant-based Alkaloids: Clinical Trialsmentioning

confidence: 99%

“…It is noteworthy that homoharringtonine was approved by the Food and Drug Administration for the treatment of patients with chronic myeloid leukemia (Q. Wang et al, 2017b ). Recently, Chen X. et al (2019) , in a randomized clinical trial, it was concluded that homoharringtonine was more efficient in the treatment of children younger than 2 years with de novo acute myeloid leukemia than standard regimen chemotherapy using anthracyclines.…”

Section: Anticancer Plant-based Alkaloids: Clinical Trialsmentioning

confidence: 99%

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Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids

2021

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Cancer is a complex multifactorial disease that results from alterations in many physiological and biochemical functions. Over the last few decades, it has become clear that cancer cells can acquire multidrug resistance to conventional anticancer drugs, resulting in tumor relapse. Thus, there is a continuous need to discover new and effective anticancer drugs. Natural products from plants have served as a primary source of cancer drugs and continue to provide new plant-derived anticancer drugs. The present review describes plant-based alkaloids, which have been reported as active or potentially active in cancer treatment within the past 4 years (2017–2020), both in preclinical research and/or in clinical trials. In addition, recent insights into the possible molecular mechanism of action of alkaloid prodrugs naturally present in plants are also highlighted.

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“…Homoharringtonine (HHT) exerts apoptotic effects against acute lymphoblastic leukemia (ALL) cells and chronic myeloid leukemia (CML) cells by decreasing expression of B cell lymphoma-6 (Bcl-6) (Wang et al, 2017). It decreases the tumorigenic potential of gefitinib-resistant non-small cell lung cancer cells (Cao et al, 2015), inhibits infiltration of mast tumor cells harboring imatinib-resistant D814Y KIT proto-oncogene (Jin et al, 2010), and proliferation of triple-negative breast cancer cells by decreasing the expression levels of B cell lymphoma-2 (Bcl-2), survivin, and X-linked inhibitor of apoptosis protein (XIAP) (Yakhni et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Homoharringtonine Inhibits Allergic Inflammations by Regulating NF-κB-miR-183-5p-BTG1 Axis

Kim

Kwon

et al. 2020

Front. Pharmacol.

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Homoharringtonine (HHT) is a drug for treatment of chronic myeloid leukemia. However, the role of HHT in allergic inflammations remains unknown. Mouse model of atopic dermatitis (AD) induced by 2, 4,-dinitroflurobenzene (DNFB) and anaphylaxis employing 2,4-dinitropheny-human serum albumin (DNP-HSA) were used to examine the role of HHT in allergic inflammations. HHT inhibited in vitro allergic reactions and attenuated clinical symptoms associated with AD. DNFB induced features of allergic reactions in rat basophilic leukemia (RBL2H3) cells. HHT suppressed effect of AD on the expression of Th1/Th2 cytokines. HHT inhibited passive cutaneous anaphylaxis and passive systemic anaphylaxis. MiR-183-5p, increased by antigen stimulation, was downregulated by HHT in RBL2H3 cells. MiR-183-5p inhibitor suppressed anaphylaxis and AD. B cell translocation gene 1 (BTG1) was shown to be a direct target of miR-183-5p. BTG1 prevented antigen from inducing molecular features of in vitro allergic reactions. AD increased the expression of NF-kB, and NF-kB showed binding to the promoter sequences of miR-183-5p. NF-kB and miR-183 formed positive feedback to mediate in vitro allergic reactions. Thus, HHT can be an anti-allergy drug. We present evidence that NF-kB-miR-183-5p-BTG1 axis can serve as target for development of anti-allergy drug.

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Homoharringtonine suppresses imatinib resistance via the Bcl-6/p53 pathway in chronic myeloid leukemia cell lines

Cited by 13 publications

References 33 publications

TMEM16A, a Homoharringtonine Receptor, as a Potential Endogenic Target for Lung Cancer Treatment

TMEM16A, a Homoharringtonine Receptor, as a Potential Endogenic Target for Lung Cancer Treatment

Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids

Homoharringtonine Inhibits Allergic Inflammations by Regulating NF-κB-miR-183-5p-BTG1 Axis

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