Erianin inhibits the oncogenic properties of hepatocellular carcinoma via inducing DNA damage and aberrant mitosis

Dong, Heng; Wang, Menglan; Chang, Cunjie; Sun, Mengqing; Yang, Fan; Li, Lina; Feng, Mengqing; Zhang, Lele; Li, Qian; Zhu, Yannan; Qiao, Yiting; Xie, Tian; Chen, Jianxiang

doi:10.1016/j.bcp.2020.114266

Cited by 28 publications

(27 citation statements)

References 35 publications

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“…Erianin at nanomolar level inhibited colony formation in both LNCaP and PC3 cells (Figures 1A, B), which is consistent with previous reports in other cancer types (12,14,17,19,20). However, in contrast to the reported inhibitory effects on cancer cell migration (17,19,20), erianin at 12.5 and 25 nM failed to suppress cell migration in both PCa cell lines (Figures 1C, D).…”

Section: Discussionsupporting

confidence: 91%

“…Many phytochemicals induce cell cycle arrest in cancers with minimal toxicity and are considered an alternative approach in cancer treatment (73). In previous studies, erianin has been shown to induce cell cycle arrest at the G2/M phase, which is associated with apoptosis (12,14,16,19). We also found that treatment with erianin caused a significant increase in the G2/M proportion of PC3 cells, where apoptosis was absent (Figures 4, 5A, B).…”

Section: Discussionsupporting

confidence: 60%

“…Having demonstrated that erianin induced G2/M arrest, we further interrogated if cells failed to enter the M phase or encountered aberrant mitosis. There have been only two studies attempting to address this question, which drew inconsistent conclusions in different cell types (12,14). We found that erianin increased expression levels of cyclin b1 and phospho-CDK1 substrates (Figure 5C), which are essential factors driving the G2-to-M transition (74,75).…”

Section: Discussionmentioning

confidence: 86%

“…Erianin is a major bibenzyl compound extracted from Dendrobium. This phytochemical has little toxicity in immortalized normal human hepatocytes and nasopharyngeal normal primary cells (12,13), whereas it has shown potent anti-tumor effects at nanomolar concentrations. Erianin induces oxidative stress, leading to apoptosis via the intrinsic apoptosis pathway (14)(15)(16)(17)(18), blocks the cell cycle at the G2/M phase (12,14,17), and has been recently found to trigger ferroptosis, an iron-dependent programmed cell death (19).…”

Section: Introductionmentioning

confidence: 99%

“…This phytochemical has little toxicity in immortalized normal human hepatocytes and nasopharyngeal normal primary cells (12,13), whereas it has shown potent anti-tumor effects at nanomolar concentrations. Erianin induces oxidative stress, leading to apoptosis via the intrinsic apoptosis pathway (14)(15)(16)(17)(18), blocks the cell cycle at the G2/M phase (12,14,17), and has been recently found to trigger ferroptosis, an iron-dependent programmed cell death (19). In addition, treatment of nude mice with erianin significantly inhibit the growth of lung cancer, osteosarcoma, colorectal cancer and bladder cancer xenografts (14,16,17,(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

et al. 2021

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Prostate cancer is the second most prevalent malignancy worldwide. In the early stages, the development of prostate cancer is dependent on androgens. Over time with androgen deprivation therapy, 20% of prostate cancers progress to a castration-resistant form. Novel treatments for prostate cancers are still urgently needed. Erianin is a plant-derived bibenzyl compound. We report herein that erianin exhibits anti-tumor effects in androgen-sensitive and castration-resistant prostate cancer cells through different mechanisms. Erianin induces endoplasmic reticulum stress-associated apoptosis in androgen-sensitive prostate cancer cells. It also triggers pro-survival autophagic responses, as inhibition of autophagy predisposes to apoptosis. In contrast, erianin fails to induce apoptosis in castration-resistant prostate cancer cells. Instead, it results in cell cycle arrest at the M phase. Mechanistically, C16 ceramide dictates differential responses of androgen-sensitive and castration-resistant prostate cancer cells to erianin. Erianin elevates C16 ceramide level in androgen-sensitive but not castration-resistant prostate cancer cells. Overexpression of ceramide synthase 5 that specifically produces C16 ceramide enables erianin to induce apoptosis in castration-resistant prostate cancer cells. Our study provides both experimental evidence and mechanistic data showing that erianin is a potential treatment option for prostate cancers.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

et al. 2021

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Design, Synthesis, and Biological Evaluation of Histone Deacetylase Inhibitors Derived from Erianin and Its Derivatives

et al. 2023

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Multi-target histone deacetylase (HDAC) inhibitors can be designed by introducing dominant structures of natural products to enhance activity and efficacy while avoiding the toxicity from other targets. In this study, we reported a series of novel HDAC inhibitors based on erianin and amino erianin upon pharmacophore fusion strategy. Two representative compounds, N-hydroxy-2-(2-methoxy-5-(3,4,5-trimethoxyphenethyl)phenoxy)acetamide and N-Hydroxy-8-((2-methoxy-5-(3,4,5-trimethoxyphenethyl)phenyl)amino)octanamide, possessed good inhibitory effect against five cancer cells tested (IC 50 = 0.30-1.29 μΜ, 0.29-1.70 μΜ) with strong HDAC inhibition, and low toxicity toward L02 cells, which were selected for subsequent biological studies in PANC-1 cells. They were also found to promote the intracellular generation of reactive oxygen species, cause DNA damage, block the cell cycle at G2/ M phase, and activate the mitochondria-related apoptotic pathway to induce cell apoptosis, which are significant for the discovery of new HDAC inhibitors.

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PARP7i Clinical Candidate RBN‐2397 Exerts Antiviral Activity by Modulating Interferon‐β Associated Innate Immune Response in Macrophages

Du,

Zhou,

Zhou

et al. 2024

Drug Development Research

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Polyadenosine diphosphate‐ribose polymerase 7 (PARP7) acts as a suppressor of the type I interferon (IFN) signaling pathway via suppressing TANK‐binding protein 1 (TBK1). Research study indicates that inhibition of PARP7 could potentially regulate tumor immunity. However, the effect of PARP7 inhibition on innate antiviral immunity in macrophages as well as the underlying mechanism have not been demonstrated else well. We report herein that PARP7 inhibitor clinical candidate RBN‐2397 could augment type I interferon (IFN‐I) production in macrophages by elevating retinoic acid‐inducible gene I (RIG‐I) and stimulator of interferon genes (STING) signaling pathways. Treatment with RBN‐2397 leads to increased pattern recognition ligands‐induced interferon‐β production in primary bone marrow‐derived macrophages (BMDM) and RAW264.7 cells. Additionally, RBN‐2397 suppresses viral replication efficiency in macrophages infected by vesicular stomatitis virus (VSV) and amplifies the expression of interferon‐stimulated chemokine genes (ISGs). Mechanistically, RBN‐2397 promotes TBK1 phosphorylation, consequently leading to the amplified activation of RIG‐I and STING signaling pathways. Furthermore, RBN‐2397 enhances the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT2 induced by IFN‐α/β and the expression of chemokine genes in macrophages in response to IFN stimulation. In vivo experiments demonstrated that RBN‐2397 enhances innate antiviral immunity in mice infected with VSV, resulting in increased serum IFN‐β levels, reduced viral loads, and alleviated pulmonary inflammatory responses of the VSV‐infected mice. In conclusion, our findings highlight the potential of RBN‐2397 as a promising antiviral therapeutic agent for enhancing the IFN‐relative antiviral immune defense in host.

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Erianin inhibits the oncogenic properties of hepatocellular carcinoma via inducing DNA damage and aberrant mitosis

Cited by 28 publications

References 35 publications

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

Design, Synthesis, and Biological Evaluation of Histone Deacetylase Inhibitors Derived from Erianin and Its Derivatives

PARP7i Clinical Candidate RBN‐2397 Exerts Antiviral Activity by Modulating Interferon‐β Associated Innate Immune Response in Macrophages

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