Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA

Liu, Xiaojiang; Zhang, Yaru; Wu, Siqi; Xu, Min; Shen, Youfeng; Yu, Min; Fan, Jinjiang; Wei, Sijia; Xu, Chaohang; Zhao, Han; Li, Xuegang; Yang, Xiaoli

doi:10.1016/j.bcp.2020.113933

Cited by 28 publications

(15 citation statements)

References 40 publications

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“…Palmatine has been widely used in clinical treatment for inflammation, dysentery, jaundice, hypertension and liverrelated diseases (Zhang et al, 2012). In addition, studies (Hambright et al, 2015;Ishikawa et al, 2016;Chakravarthy et al, 2018;Johnson-Ajinwo et al, 2019) have shown that palmatine has certain therapeutic benefits for pancreatic cancer, osteoporosis, prostate cancer, ovarian cancer and colon cancer (Liu et al, 2020b). Our work revealed that 2 weeks after the treatment of TN rats with palmatine, the reduced mechanical pain threshold was significantly increased, indicating that palmatine could alleviate the neuropathic pain caused by TN.…”

Section: Discussionmentioning

confidence: 50%

Inhibitory Effects of Palmatine on P2X7 Receptor Expression in Trigeminal Ganglion and Facial Pain in Trigeminal Neuralgia Rats

Yin

WenHao

Zhang

et al. 2021

Front. Cell. Neurosci.

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Trigeminal Neuralgia (TN) refers to recurrent severe paroxysmal pain in the distribution area of the trigeminal nerve, which seriously affects the quality of life of patients. This research applied the chronic constriction injury of the infraorbital nerve (CCI—ION) approach to induce an animal model of TN in rats. The mechanical pain threshold of each group of rats was determined postoperatively; the expression of P2X7 receptor in trigeminal ganglion (TG) was assessed by qRT-PCR, immunofluorescence and Western blot; and the changes of the proinflammatory cytokines IL-1β and TNF-α in serum of rats were detected by ELISA. The results showed that the administration of palmatine in the TN rats could reduce the mechanical pain threshold, significantly decrease the expression of P2X7 receptor in TG, and lower the serum concentrations of IL-1β and TNF-α, compared to the sham group. In addition, the phosphorylation level of p38 in TG of TN rats was significantly decreased after treatment with palmatine. Likewise, inhibition of P2X7 expression by shRNA treatment could effectively counteract the adversary changes of pain sensitivity, IL-1β and TNF-α production, and p38 phosphorylation in TN rats. Our data suggest that palmatine may alleviate mechanical facial pain in TN rats possibly by reducing the expression of P2X7 receptor in TG of TN rats, which may be attributable to inhibiting p38 phosphorylation and reducing the release of IL-1β and TNF-α.

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Section: Discussionmentioning

confidence: 50%

Inhibitory Effects of Palmatine on P2X7 Receptor Expression in Trigeminal Ganglion and Facial Pain in Trigeminal Neuralgia Rats

Yin

WenHao

Zhang

et al. 2021

Front. Cell. Neurosci.

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“…Previous studies showed that AURKA participated in various carcinogenic processes [45,46], including suppressing DNA damage repair and antagonizing apoptosis [47][48][49]. Indeed, its targeted inhibitor has entered clinical phase II or phase III studies in the treatment of tumors [50,51], which also emphasizes the promising prospect of AURKA inhibition by Mibefradil in TNBC therapy.…”

Section: Discussionmentioning

confidence: 99%

Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

Han

Liu³

et al. 2021

Preprint

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Background: Triple negative breast cancer (TNBC) is a tumor characterized by high recurrence and mortality, but without effective targeted therapy. It is urgent to explore new treatment strategy to improve the efficacy of TNBC therapy. Methods: Transcriptomic profiling datasets of TNBC were used for screening TNBC specific gene sets. Drug prediction was performed in Connectivity map (CMap) database. Molecular docking method was used for analyzing drug targets. In vitro and in vivo models of TNBC were constructed to examine the drug efficacy. Results: We screened out Mibefradil, a T-type Ca2+ channel blocker, might be a potential therapeutic drug for TNBC by transcriptomics and bioinformatics analysis, and verified that Mibefradil could inhibit the proliferation of TNBC cells by inducing apoptosis and cell cycle arrest. Furthermore, by network pharmacology and molecular docking analysis, AURKA was predicted as the most possible drug target of Mibefradil. Finally, it was proved that Mibefradil treatment could induce apoptosis by decreasing protein expression and phosphorylation level of AURKA in vitro and in vivo. Conclusions: Mibefradil played anti-cancer role in TNBC cells by targeting to AURKA to induce cell cycle and apoptosis. Our results repurposed Mibefradil as a potential targeted drug of TNBC and provided a fundamental research for a novel strategy TNBC treatment.

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“…Aurora A (also known as serine/threonine protein kinase 15) serves a role in mitosis and meiosis by regulating the phosphorylation of specific substrates, and its activity is the highest during G 2 /S phase transition ( 76 ). Aurora A is overexpressed in a variety of tumors, resulting in abnormal centrosome expansion, increased chromosomal instability and eventual carcinogenic transformation ( 76 , 77 ). FBXW7-deficient HCT116 and HeLa cells exposed to vincristine, paclitaxel and spindle toxin exhibit extensive mitotic delay and nuclear duplication, which are important causes of polyploidy.…”

Section: Substrates and Mechanisms Of Fbxw7 Involved In Tumor Suppresmentioning

confidence: 99%

Function and regulation of F‑box/WD repeat‑containing protein 7 (Review)

Zhang

et al. 2020

Oncol Lett

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The ubiquitin-proteasome system is an important post-translational modification system involved in numerous biological processes, such as cell cycle regulation, gene transcription, signal transduction, apoptosis, differentiation and development. F-box/WD repeat-containing protein 7 (FBXW7) is one of the most studied F-box (FBX) proteins, serving as substrate recognition component of S phase kinase-associated protein 1-Cullin 1-FBX protein complexes. As a tumor suppressor, FBXW7 recognizes numerous proto-oncoproteins and promotes their ubiquitination and subsequent proteasomal degradation. FBXW7 is regulated at different levels, leading to tunable and specific control of the activity and abundance of its substrates. Therefore, genetic mutations or decreases in its expression serve an important biological role in tumor development. In-depth studies and identification of additional substrates targeted by FBXW7 have suggested a signaling network regulated by FBXW7, including its tumor-inhibitory role. The present review focused on the role of FBXW7 in tumor suppression and its application in cancer therapy. Contents 1. Introduction 2. Transcriptional and translational regulation of FBXW7 expression 3. Post-translational modifications of FBXW7 4. Genetic alterations of FBXW7 in cancers 5. Substrates and mechanisms of FBXW7 involved in tumor suppression 6. Therapeutic exploitation of FBXW7 signaling 7. Conclusions

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Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA

Cited by 28 publications

References 40 publications

Inhibitory Effects of Palmatine on P2X7 Receptor Expression in Trigeminal Ganglion and Facial Pain in Trigeminal Neuralgia Rats

Inhibitory Effects of Palmatine on P2X7 Receptor Expression in Trigeminal Ganglion and Facial Pain in Trigeminal Neuralgia Rats

Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

Function and regulation of F‑box/WD repeat‑containing protein 7 (Review)

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