Repression of Noxa by Bmi1 contributes to deguelin‐induced apoptosis in non‐small cell lung cancer cells

Li, Wei; Yu, Xinfang; Xia, Zhenkun; Yu, Xinyou; Xie, Li; Ma, Xiaolong; Zhou, Huiling; Liu, Lijun; Wang, Jian; Yang, Yifeng; Liu, Haidan

doi:10.1111/jcmm.13908

Cited by 32 publications

(32 citation statements)

References 59 publications

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“…MTS assays. MTS assay was performed as described previously (17). Briefly, human OSCC cells were seeded in 96-well plates at a concentration of 2×10 3 /well.…”

Section: Methodsmentioning

confidence: 99%

Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma

Gao

et al. 2020

Preprint

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Background: Overexpression of survivin plays a crucial role in the maintaining unlimited cell growth, apoptosis suppression, and correlates with poor prognosis in human malignancies. Methods: A natural product library was used for natural compound screening through MTS assay. The expression of survivin in oral squamous cell carcinoma (OSCC) and the inhibitory effect of xanthohumol (XN) on OSCC were examined through methods of anchorage-dependent and -independent growth assays, immunoblot, immunofluorescence, immunohistochemical staining, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiment. Results: Survivin is highly expressed in OSCC cells and patient-derived tissues, and required for OSCC cell growth in vitro and in vivo . With a natural compound screening, we identified that xanthohumol exhibited a significant anti-tumor effect against OSCC cells through inhibiting survivin protein. Xanthohumol suppressed anchorage-dependent and independent cell growth and delayed in vivo tumor development of OSCC cells. Xanthohumol inhibited the Akt-Wee1-CDK1 signaling, which in turn decreased survivin phosphorylation on Thr34, and facilitated E3 ligase Fbxl7-mediated survivin ubiquitination. Xanthohumol alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Conclusion: Our findings indicate that targeting survivin for degradation might a promising strategy for OSCC treatment. Keywords: Oral squamous cell carcinoma; Xanthohumol; Ubiquitination; Fbxl7

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“…MTS assays. MTS assay was performed as described previously (17). Briefly, human OSCC cells were seeded in 96-well plates at a concentration of 2×10 3 /well.…”

Section: Methodsmentioning

confidence: 99%

Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma

Gao

et al. 2020

Preprint

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“…Accumulating evidence reveals that the natural product deguelin exhibits profound anti-cancer potentials in multiple human cancer models, including lung cancer 14 , hepatocellular carcinoma 15 , colorectal cancer 16 , esophageal carcinoma 17 , metastatic melanoma 18 , and breast cancer 19 . The molecular mechanism studies showed that delay of cell cycle progression by inhibition of Aurora B kinase, regulation of metabolisms, such as suppression of glycolysis, down-regulation of angiogenesis and metastasis, and activation of intrinsic apoptosis were related to deguelin-mediated anti-tumor effect [20][21][22] . However, the effect of deguelin on EGFR signaling, as well as its inhibitory efficacy on both gefitinib sensitive and resistant cells, was not clear.…”

Section: Introductionmentioning

confidence: 99%

Deguelin suppresses non-small cell lung cancer by inhibiting EGFR signaling and promoting GSK3β/FBW7-mediated Mcl-1 destabilization

Gao

et al. 2020

Cell Death Dis

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Activating mutations of epidermal growth factor receptor (EGFR) play crucial roles in the oncogenesis of human nonsmall cell lung cancer (NSCLC). By screening 79 commercially available natural products, we found that the natural compound deguelin exhibited a profound anti-tumor effect on NSCLC via directly down-regulating of EGFR-signaling pathway. Deguelin potently inhibited in vitro EGFR kinase activity of wild type (WT), exon 19 deletion, and L858R/ T790M-mutated EGFR. The in silico docking study indicated that deguelin was docked into the ATP-binding pocket of EGFRs. By suppression of EGFR signaling, deguelin inhibited anchorage-dependent, and independent growth of NSCLC cell lines, and significantly delayed tumorigenesis in vivo. Further study showed that deguelin inhibited EGFR and downstream kinase Akt, which resulted in the activation of GSK3β and eventually enhanced Mcl-1 phosphorylation at S159. Moreover, deguelin promoted the interaction between Mcl-1 and E3 ligase SCF FBW7 , which enhanced FBW7-mediated Mcl-1 ubiquitination and degradation. Additionally, phosphorylation of Mcl-1 by GSK3β is a prerequisite for FBW7-mediated Mcl-1 destruction. Depletion or pharmacological inactivation of GSK3β compromised deguelin-induced Mcl-1 ubiquitination and reduction. Taken together, our data indicate that enhancement of ubiquitination-dependent Mcl-1 turnover might be a promising approach for cancer treatment.

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“…In contrast to the small molecule through rational chemical design, natural products have more potential to be applied to tumor chemotherapy owing to their structural diversity. Recently, numerous natural compounds have been demonstrated exerting anti-tumor activity through the suppression of cell cycle progression, impairment of angiogenesis, induction of apoptosis, and inhibition of glycolysis [20,[29][30][31][32][33][34]. Piperlongumine is an amide alkaloid constituent of the Piper longum L. (long piper), which is also named as piplartine and used as an Ayurvedic medicine for a long time.…”

Section: Discussionmentioning

confidence: 99%

Repression of Hexokinases II-Mediated Glycolysis Contributes to Piperlongumine-Induced Tumor Suppression in Non-Small Cell Lung Cancer Cells

Zhou

Yu³

et al. 2019

Int. J. Biol. Sci.

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Deregulation of glycolysis is a common phenomenon in human non-small cell lung cancer (NSCLC). In the present study, we reported the natural compound, piperlongumine, has a profound anti-tumor effect on NSCLC via regulation of glycolysis. Piperlongumine suppressed the proliferation, colony formation and HK2-mediated glycolysis in NSCLC cells. We demonstrated that exposure to piperlongumine disrupted the interaction between HK2 and VDAC1, induced the activation of the intrinsic apoptosis signaling pathway. Moreover, our results revealed that piperlongumine down-regulated the Akt signaling, exogenous overexpression of constitutively activated Akt1 in HCC827 and H1975 cells significantly rescued piperlongumine-induced glycolysis suppression and apoptosis. The xenograft mouse model data demonstrated the pivotal role of suppression of Akt activation and HK2-mediated glycolysis in mediating the in vivo antitumor effects of piperlongumine. The expression of HK2 was higher in malignant NSCLC tissues than that of the paired adjacent tissues, and was positively correlated with poor survival time. Our results suggest that HK2 could be used as a potential predictor of survival and targeting HK2 appears to be a new approach for clinical NSCLC prevention or treatment.

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Repression of Noxa by Bmi1 contributes to deguelin‐induced apoptosis in non‐small cell lung cancer cells

Cited by 32 publications

References 59 publications

Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma

Promotion of ubiquitination-dependent survivin destruction contributes to xanthohumol-mediated tumor suppression and overcomes radioresistance in human oral squamous cell carcinoma

Deguelin suppresses non-small cell lung cancer by inhibiting EGFR signaling and promoting GSK3β/FBW7-mediated Mcl-1 destabilization

Repression of Hexokinases II-Mediated Glycolysis Contributes to Piperlongumine-Induced Tumor Suppression in Non-Small Cell Lung Cancer Cells

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