Antibiotic anisomycin selectively targets leukemia cell lines and patient samples through suppressing Wnt/β-catenin signaling

Li, Yong; Hu, Jialin; Song, Ho-Young; Wu, Tao

doi:10.1016/j.bbrc.2018.09.183

Cited by 18 publications

(25 citation statements)

References 29 publications

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“…Since cancer stem cells are resistant to most traditional chemotherapeutic drugs, such as cisplatin and paclitaxel, it is necessary to develop more effective drugs for tumour chemotherapy (21,(29)(30)(31). Anisomycin has been confirmed to have significant inhibitory effects on a variety of solid tumours and is a promising chemotherapeutic drug candidate (7)(8)(9)(10)(11). Our previous report has revealed that anisomycin inhibits the proliferation and invasion of ovarian cancer stem cells by enhancing the activity of lncRNA-BACE1-AS and increasing the release of endogenous Aβ42 (7).…”

Section: Discussionmentioning

confidence: 99%

“…The present study suggested that anisomycin may have the potential to inhibit cancer stem cells. Based on the existing reports (7)(8)(9)(10)(11), it was speculated that the inhibitory effect of anisomycin on cancer stem cells may depend on multi-target regulation. Therefore, it is meaningful to explore its in-depth mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Anisomycin [also known as 3,4-Pyrrolidinediol,2-[(4-methoxyphenyl)methyl]-,3-acetate,(2R,3S,4S)] is the first confirmed anti-protozoal antibiotic extracted from Streptomyces griseolus (7,8). Anisomycin inhibits the formation of peptide bonds in most cells by binding to the 60S ribosomal subunit and, thereby, inhibiting protein synthesis (7,8). Previous studies have shown that anisomycin can promote the production of amyloid β (Aβ) 1-42 causing neurotoxicity, as well as inhibit the proliferation of certain cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

Shen

et al. 2019

Int J Oncol

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Angiogenesis has an important role in tumour cell growth and metastasis. Anisomycin has been shown to inhibit tumour cell growth. However, whether anisomycin can inhibit angiogenesis of tumours has not been reported. The present study demonstrated that there was a positive correlation between tumour angiogenesis and the number of CD44 + /CD133 + serous human ovarian cancer stem cells (HuOCSCs). Subsequently, it was confirmed that anisomycin significantly inhibited the proliferation, invasion, tumorigenic ability and tumour angiogenesis of HuOCSCs. Gene expression profiling by cDNA microarrays revealed that the expression levels of vascular endothelial cell markers, platelet-derived growth factors, Notch pathway components and 27 tumour angiogenesis-related genes were significantly decreased in the anisomycin-treated group compared with the control group. Further experiments demonstrated that the expression levels of endogenous long non-coding RNA (lncRNA) maternally expressed 3 (Meg3) were significantly decreased in anisomycin-treated HuOCSCs, whereas the expression levels of microRNA (miR)-421 were significantly increased. The results of luciferase reporter assays indicated that, when miR-421 was overexpressed in cells, the luciferase activities of wild-type platelet derived growth factor receptor α (PDGFRA) 3' untranslated region and Meg3 reporter plasmids were significantly decreased. Overexpression of miR-421 in HuOCSCs significantly enhanced the anisomycin-mediated inhibition of HuOCSC proliferation. Taken together, the present results demonstrated that anisomycin inhibited the activation downstream of the Notch1 pathway by attenuating the molecular sponge effect of the lncRNA-Meg3/miR-421/PDGFRA axis, ultimately inhibiting angiogenesis, proliferation and invasion in ovarian cancer cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

Shen

et al. 2019

Int J Oncol

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“…BP-CML CD34 + and normal bone marrow (NBM) CD34 + cells (StemCell Technologies) were cultured using the same growth factors and cytokines supplemented serum-free medium as described in our previous study. 17 Human CML cell lines were cultured in RPMI1640 medium (Life Technologies) supplemented with 10% fetal bovine serum (Hyclone) and 2mM glutamine (Invitrogen). Imatinib (LC laboratories) was reconstituted in PBS.…”

Section: Methodsmentioning

confidence: 99%

“…Cell proliferative and apoptotic activities were determined using the same methods as described in our previous study. 17 Colony-Forming and Serial Replating Assays CD34 + cells at 1000/well together with drugs were mixed with HSC-CFU methylcellulose medium (Miltenyi Biotec) and plated onto 6-well plate. After 2 weeks incubation, colonies were formed and counted.…”

Section: Measurement Of Proliferation and Apoptosismentioning

confidence: 99%

<p>Targeting of the Alox12-12-HETE in Blast Crisis Chronic Myeloid Leukemia Inhibits Leukemia Stem/Progenitor Cell Function</p>

Si¹,

Hu²,

Yong³

2020

CMAR

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Introduction: Chronic myeloid leukemia (CML) is a myeloid malignancy characterized by the oncogene BCR-ABL. CML responds well to therapy targeting BCR-ABL in the chronic phase but is resistant to treatment when it progresses to the blast phase (BP). This study attempted to address whether arachidonate 12-lipoxygenase (Alox12) confers to CML drug resistance. Materials and Methods: We analyzed the expression of Alox12 using Western blotting, ELISA, and RT-PCR methods. Loss of functional analysis was performed using cellular activity assays on CML and normal hematopoietic stem/progenitor cells (HSPCs). Results: Alox12 and 12-Hydroxyeicosatetraenoic acid (12-HETE) are overexpressed in BP-CML but not HSPCs, and that Alox12-12-HETE axis is regulated by BCR-ABL. The Alox12-12-HETE axis is required for CML. Specific Alox12 inhibitor inhibits colony formation, survival, and self-renewal capacity in BP-CML HSPCs, and to a significantly greater extent than in normal HSPCs. Of note, the Alox12 inhibitor significantly augments dasatinib's efficacy in BP-CML HSPCs. Mechanism studies show that Alox12 inhibition does not affect activities of essential signaling pathways involved in maintaining stem cell function, such as Wnt, p53, and bone morphogenetic protein (BMP). In contrast, we show that Alox12 inhibition disrupts nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis and induces oxidative stress and damage in CML HSPCs and committed cells. Conclusion: Alox12-12-HETE axis is a specific and critical regulator of BP-CML HSPCs functions. Pharmacological inhibition of Alox12 may be useful in BP-CML.

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Anisomycin inhibits the activity of human ovarian cancer stem cells via regulating antisense RNA NCBP2‐AS2/MEK/ERK/STAT3 signaling

Ling

Wen

Xiong

et al. 2023

The Journal of Gene Medicine

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BackgroundOvarian cancer stem cells (OCSCs) are the main cause of relapse and drug resistance in patients with ovarian cancer. Anisomycin has been shown to be an effective antitumor agent, but its mechanism of action in ovarian cancer remains elusive.MethodsCD44+/CD133+ human OCSCs were isolated from human ovarian cancer tissues. OCSCs were interfered with using anisomycin and specific small‐interfering RNA (siRNA). Microarray assay, MTT, in vivo tumorigenic experiments, transwell assay, cell cycle assay, colony formation assay, angiogenesis assay, and hematoxylin and eosin staining were used to detect the mechanism of anisomycin with respect to inhibiting the activity of OCSCs. Expression of the NCBP2‐AS2/mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) pathway was examined using western blotting, a quantitative real‐time PCR (RT‐qPCR) and immunofluorescence staining. Bioinformatics analysis was used for predictive analysis of NCBP2‐AS2 expression in urogenital tumors.ResultsMicroarray analysis showed that treatment with anisomycin significantly decreased the expression of antisense RNA NCBP2‐AS2 in OCSCs. In vitro cellular experiments showed that interfering with endogenous antisense RNA NCBP2‐AS2 using siRNA distinctly inhibited the proliferation, migration and angiogenesis of OCSCs, whereas in vivo animal experiments revealed decreased tumorigenesis in nude mice. Moreover, the results of RT‐qPCR and western blotting demonstrated that both anisomycin treatment and NCBP2‐AS2 silencing led to significant reductions in the mRNA and protein expression levels of NCBP2‐AS2, MEK, ERK and STAT3. From a bioinformatic point of view, antisense RNA NCBP2‐AS2 exhibited significantly differential expression between urogenital tumors and normal controls, and a similar expression pattern was found in the genes NCBP2, RPL35A, DNAJC19 and ECE2, which have similarity to NCBP2‐AS2.ConclusionsAnisomycin suppresses the in vivo and in vitro activity of human OCSCs by downregulating the antisense RNA NCBP2‐AS2/MEK/ERK/STAT3 signaling pathway, whereas the antisense RNA NCBP2‐AS2 and genes with similarity have the potential to serve as markers for clinical diagnosis and prognosis of urogenital tumors.

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Antibiotic anisomycin selectively targets leukemia cell lines and patient samples through suppressing Wnt/β-catenin signaling

Cited by 18 publications

References 29 publications

Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

<p>Targeting of the Alox12-12-HETE in Blast Crisis Chronic Myeloid Leukemia Inhibits Leukemia Stem/Progenitor Cell Function</p>

Anisomycin inhibits the activity of human ovarian cancer stem cells via regulating antisense RNA NCBP2‐AS2/MEK/ERK/STAT3 signaling

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