Nitidine chloride possesses anticancer property in lung cancer cells through activating Hippo signaling pathway

Zhang, Jing; Wu, Linhui; Lian, Chaoqun; Lian, Shuo; Bao, Shimeng; Zhang, Jisheng; Wang, Z. Peter; Ma, Jia; Li, Yuyun

doi:10.1038/s41420-020-00326-7

Cited by 19 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In brief, the cells were seeded in a 96-well plate and transfected with plasmids for 4 h, and then the culture media were replaced and cultured for an additional 24 or 48 h. A 10 μL CCK-8 reagent was added to each well and incubated at 37 °C for 2 h. The absorbance at OD450 was detected by the Multiskan™ FC Microplate Photometer (Thermo Fisher). The transwell assays were conducted as previously reported [ 34 ]. The upper chamber was pre-treated with Matrigel matrix (#354230, BD, USA).…”

Section: Methodsmentioning

confidence: 99%

PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

et al. 2021

View full text Add to dashboard Cite

Emerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.

show abstract

Section: Methodsmentioning

confidence: 99%

PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This natural bioactive alkaloid is capable of inhibiting the malignant behavior of GBM through suppression of EMT and stem cell-like properties by modulation of the JAK2/STAT3 signaling pathway [209] and through targeting of PI3K/AKT/mTOR signaling pathway [210]. Lately, NC has been reported to have anticancer properties by activating the Hippo pathway in lungs cancer cells [211], thereby could be interesting to further investigate if NC may have a role in the activation of the Hippo signaling even in glioma cells (Table 3).…”

Section: Hippo Pathway and Glioblastoma: Pharmacological Interventionsmentioning

confidence: 99%

Hippo Pathway in Regulating Drug Resistance of Glioblastoma

Casati

Giunti

Iorio

et al. 2021

IJMS

View full text Add to dashboard Cite

Glioblastoma (GBM) represents the most common and malignant tumor of the Central Nervous System (CNS), affecting both children and adults. GBM is one of the deadliest tumor types and it shows a strong multidrug resistance (MDR) and an immunosuppressive microenvironment which remain a great challenge to therapy. Due to the high recurrence of GBM after treatment, the understanding of the chemoresistance phenomenon and how to stimulate the antitumor immune response in this pathology is crucial. The deregulation of the Hippo pathway is involved in tumor genesis, chemoresistance and immunosuppressive nature of GBM. This pathway is an evolutionarily conserved signaling pathway with a kinase cascade core, which controls the translocation of YAP (Yes-Associated Protein)/TAZ (Transcriptional Co-activator with PDZ-binding Motif) into the nucleus, leading to regulation of organ size and growth. With this review, we want to highlight how chemoresistance and tumor immunosuppression work in GBM and how the Hippo pathway has a key role in them. We linger on the role of the Hippo pathway evaluating the effect of its de-regulation among different human cancers. Moreover, we consider how different pathways are cross-linked with the Hippo signaling in GBM genesis and the hypothetical mechanisms responsible for the Hippo pathway activation in GBM. Furthermore, we describe various drugs targeting the Hippo pathway. In conclusion, all the evidence described largely support a strong involvement of the Hippo pathway in gliomas progression, in the activation of chemoresistance mechanisms and in the development of an immunosuppressive microenvironment. Therefore, this pathway is a promising target for the treatment of high grade gliomas and in particular of GBM.

show abstract

“…Natural compounds are an abundant source for the discovery of anti-cancer agents such as vincristine, vinblastine, paclitaxel, curcumin, colchicine and lycopene [28,29]. Lots of studies has reported NC exerted good efficacies for a variety of cancer by inducing apoptosis and autophagy [14,15,30]. In the present study, we observed that pretreatment with the apoptosis inhibitor (Z-VAD-FMK) or pyroptosis inhibitor (DSF) partly increased the cell viability after NC treatment rather than IM-54, nec-1, or fer-1.…”

Section: Discussionmentioning

confidence: 99%

Nitidine chloride induces caspase 3/GSDME-dependent pyroptosis by inhibting PI3K/Akt pathway in lung cancer

Tan

Chen

et al. 2022

Chin Med

View full text Add to dashboard Cite

Background As the increasing mortality and incidence of lung cancer (LC), there is an urgent need to discover novel treatment agent. In this study, we aimed to investigate the anti-LC effects of nitidine chloride (NC), a small molecular compound extracted from Chinese herbal medicine, while detailing its underlying mechanisms. Methods Cell viability was detected by MTT assays and five cell death inhibitors, including ferrostatin-1 (Fer-1), Z-VAD-FMK, necrostatin-1 (Nec-1), disulfiram (DSF) and IM-54 were used to explore the type of cell death induced by NC. The microscopic features of NC-induced pyroptosis were assessed by transmission electron microscopy (TEM) and the pyroptotic-related proteins such as caspase and gasdermin family, were examined by western blot. Network pharmacology was employed to predict the potential mechanisms of NC in lung cancer treatment. CETSA and DARTs were used to determine the activity of NC binding to targeted protein. Xenograft mice model was established to further investigate the inhibitory effect and mechanism of NC against LC. Results The pyroptosis inhibitor (DSF) and apoptosis inhibitor (Z-VAD-FMK) but not IM-54, necrostatin-1, or Ferrostatin-1 rescued NC-induced cell death. Morphologically, H1688 and A549 cells treated with NC showed notably pyroptotic features, such as cell swelling and large bubbles emerging from the plasma membrane. Gasdermin E (GSDME) rather than GSDMC or GSDMD was cleaved in NC-treated H1688 and A549 cells with an increased cleavage of caspase 3. Combined with network pharmacology and molecule docking, PI3K/Akt signaling axis was predicted and was further verified by CETSA and DARTs assay. In addition, the activation of PI3K is able to rescue the pyroptosis induced by NC in vitro. In xenograft model of LC, NC significantly hindered the transduction of PI3K-AKT pathway, inducing pyroptosis of tumor. Conclusion Our data indicated that NC is a potential therapeutic agent for the treatment of LC via triggering GSDME-dependent pyroptosis.

show abstract

Nitidine chloride possesses anticancer property in lung cancer cells through activating Hippo signaling pathway

Cited by 19 publications

References 34 publications

PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

Hippo Pathway in Regulating Drug Resistance of Glioblastoma

Nitidine chloride induces caspase 3/GSDME-dependent pyroptosis by inhibting PI3K/Akt pathway in lung cancer

Contact Info

Product

Resources

About