YAP Inhibition by Nuciferine via AMPK-Mediated Downregulation of HMGCR Sensitizes Pancreatic Cancer Cells to Gemcitabine

Zhou, Ling; Wang, Qiaoyun; Zhang, Han; Li, Youjie; Xie, Songqiang; Xu, Maolei

doi:10.3390/biom9100620

Cited by 28 publications

(14 citation statements)

References 38 publications

(45 reference statements)

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“… 8 − 10 Some studies confirmed that the safety, effectiveness, and multitarget characteristics of TCM have significant advantages in the treatment of ischemic stroke. 11 − 13 …”

Section: Introductionmentioning

confidence: 99%

UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals the Anti-Ischemic Stroke Mechanism of Nuciferine in MCAO Rats

Chang

et al. 2020

ACS Omega

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Nuciferine is an aporphine alkaloid monomer that is extracted from the leaves of the lotus species Nymphaea caerulea and Nelumbo nucifera Gaertn. Nuciferine was reported to treat cerebrovascular diseases. However, the potential mechanism of the neuroprotective effects of nuciferine at the metabolomics level is still not unclear. The present research used neurological score, infarct volume, cerebral water content, and ultraperformance liquid chromatography to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based serum metabolomics to elucidate the anti-ischemic stroke effect and mechanisms of nuciferine. The results showed that nuciferine significantly improved neurological deficit scores and ameliorated cerebral edema and infarction. Multivariate data analysis methods were used to examine the differences in serum endogenous metabolism between groups, and the biomarkers of nuciferine on ischemic stroke were identified. Approximately 19 metabolites and 7 metabolic pathways associated with nuciferine on treatment of stroke were found, which indicated that nuciferine exerted a positive therapeutic action on cerebral ischemic by regulating metabolism. These results provided some data support for the study of anti-stroke effect of nuciferine from the perspective of metabolomics.

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“… 8 − 10 Some studies confirmed that the safety, effectiveness, and multitarget characteristics of TCM have significant advantages in the treatment of ischemic stroke. 11 − 13 …”

Section: Introductionmentioning

confidence: 99%

UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals the Anti-Ischemic Stroke Mechanism of Nuciferine in MCAO Rats

Chang

et al. 2020

ACS Omega

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“…As an essential cellular pathway, AMPK signaling widely participates in the regulation of gemcitabine resistance of PDAC. It has been reported that the inhibition of YAP by AMPK-regulated HMGCR downregulation is able to sensitize gemcitabine resistance of PDAC cells 27 . Gemcitabine promotes autophagy and apoptosis by the AMPK signaling in PDAC 28 .…”

Section: Discussionmentioning

confidence: 99%

SLC39A1 Contributes to Gemcitabine Resistance of Pancreatic Ductal Adenocarcinoma by Activating AMPK Signaling

Mei

Zhang

et al. 2021

Preprint

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Objective: Pancreatic ductal adenocarcinoma (PDAC) serves as a prevailing tumor type with high mortality and poor prognosis. The study aims to explore the mechanism of gemcitabine resistance in PDAC patients. Methods: Immunohistochemistry(IHC)was used to analyze the expression of SLC39A1 in PDAC samples. PDAC cells were culture and transfected with siSLC39A1 and siNC, respectively. Cell proliferation analysis was performed using CCK-8 assay. And qPCR and Western blotting was used to analysis the expression level of SLC39A1 and related signal molecular in cells. Results: IHC results demonstrated that the SLC39A1 expression was significantly up-regulated in the gemcitabine-resistant PDAC samples compared with gemcitabine-sensitive PDAC samples. The treatment of gemcitabine dose-dependently inhibited the viability of the PDAC cells. Meanwhile, the mRNA and protein expression of SLC39A1 were elevated in the gemcitabine-resistant PDAC. The treatment of gemcitabine remarkably decreased viability of PDACs, in which SLC39A1 depletion could reverse this effect. SLC39A1 knockdown could reverse the gemcitabine-induced phosphorylation of AMPK enhanced and gemcitabine-inhibited S6K expression. Conclusion: SLC39A1 contributed to gemcitabine resistance of PDAC by activating AMPK signaling.

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“…Qi et al (2016) found that nuciferine may be as a novel anti-cancer agent in colorectal cancer and neuroblastoma by using a traditional Chinese medicine network pharmacology method. Zhou et al (2019a) also found that application of nuciferine could sensitize pancreatic cancer cells to gemcitabine by inhibiting YAP. Nuciferine was also reported to display anti-tumor activities in glioblastoma, non-small cell lung cancer and breast cancer (Liu et al 2015;Kang et al 2017;Li et al 2019).…”

Section: Introductionmentioning

confidence: 94%

Tripartite Motif-Containing 44 is Involved in the Tumorigenesis of Laryngeal Squamous Cell Carcinoma, and its Expression is Downregulated by Nuciferine

Sui

Zhao

et al. 2021

Tohoku J. Exp. Med.

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Tripartite motif-containing 44 (TRIM44) was reported to be involved in the tumorigenesis of several tumors, but its function in laryngeal squamous cell carcinoma has not been investigated yet. In the present study, we aimed to elucidate the function of TRIM44 in laryngeal squamous cell carcinoma, and identify the compounds which could inhibit TRIM44 expression. Our results showed that TRIM44 was upregulated in tumor tissues and cell lines of laryngeal squamous cell carcinoma. Knockdown of TRIM44 significantly inhibited cell growth of laryngeal squamous cell carcinoma by suppressing TLR4, phosphorylated AKT and phosphorylated NF-κB p65 expression in vitro. Moreover, TRIM44 knockdown inhibited tumor growth in nude mice, which further suggested that TRIM44 exerted oncogenic activity in laryngeal squamous cell carcinoma. Interestingly, it was found that nuciferine significantly inhibited the mRNA levels of TRIM44 after screening a small natural compound library. Our further studies showed nuciferine markedly downregulated the protein levels of TRIM44 and its substrate TLR4 in a concentration-dependent manner in laryngeal squamous cell carcinoma cells. Moreover, the activation of downstream kinases of TLR4 such as AKT signaling pathway was also inhibited by nuciferine. Additionally, nuciferine markedly inhibited cell survival of laryngeal squamous cell carcinoma in a concentration-dependent manner. In contrast, TRIM44 overexpression significantly reduced the cytotoxicity of nuciferine in laryngeal squamous cell carcinoma cells. In conclusion, this study indicated that inhibiting TRIM44 would be a useful strategy for the treatment of laryngeal squamous cell carcinoma, and nuciferine could be a potential chemical applicated in the therapy of laryngeal squamous cell carcinoma.

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YAP Inhibition by Nuciferine via AMPK-Mediated Downregulation of HMGCR Sensitizes Pancreatic Cancer Cells to Gemcitabine

Cited by 28 publications

References 38 publications

UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals the Anti-Ischemic Stroke Mechanism of Nuciferine in MCAO Rats

UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals the Anti-Ischemic Stroke Mechanism of Nuciferine in MCAO Rats

SLC39A1 Contributes to Gemcitabine Resistance of Pancreatic Ductal Adenocarcinoma by Activating AMPK Signaling

Tripartite Motif-Containing 44 is Involved in the Tumorigenesis of Laryngeal Squamous Cell Carcinoma, and its Expression is Downregulated by Nuciferine

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