Notch signaling pathway mediates Doxorubicin-driven apoptosis in cancers

Huang, Zixin; Lin, Shuibin; Long, Chongde; Zhou, Xin; Fan, Yuting; Kuang, Xiaying; He, Jia; Ning, Jie; Zhang, Han; Zhang, Qingjiong; Shen, Huangxuan

doi:10.2147/cmar.s160315

Cited by 20 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike apoptosis, senescence is a relatively stable state with active metabolism. Doxorubicin can induce cell apoptosis in 24 h in a dose-dependent manner [24]. The time-delayed effect of doxorubicin induced cell senescence, indicating that the cell fate (apoptosis or senescence) was determined by a different mechanism.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin-Induced Cancer Cell Senescence Shows a Time Delay Effect and Is Inhibited by Epithelial-Mesenchymal Transition (EMT)

Zhang

2019

Med Sci Monit

View full text Add to dashboard Cite

Background Senescence is a natural barrier for the body to resist the malignant transformation of its own cells. This work investigated the senescence characteristics of cancer cells in vitro . Material/Methods Human cervical cancer HeLa cells were treated with different concentrations of doxorubicin for 3 days, with or without subsequent extended culture in drug-free medium for 6 days. Senescent cell ratios between these 2 culture schemes were calculated. Expression of 2 senescence-associated secretory factors, IL-6 and IL-8, were detected by RT-PCR and ELISA. Doxorubicin treatment induced epithelial-mesenchymal transition in cancer cells. The proportions of senescent cells in epithelial-like and mesenchymal-like sub-groups were calculated. Doxorubicin-treated HeLa cells were stained with Vimentin antibody and sorted by flow cytometry. Senescent cell marker p16 INK4a and IL-8 expression in Vimentin-high and Vimentin-low cells were detected by Western blot. Results We found that less than 1% of HeLa cells showed senescence phenotype after treatment with doxorubicin for 3 days. However, the proportion of senescent cells was significantly increased when the doxorubicin-treated cells were subsequently cultured in drug-free medium for another 6d. RT-PCR and ELISA results showed that this prolonged culture method could further improve the expression of IL-6 and IL-8. We also found that the senescent cells were mainly epithelial-like type and few presented mesenchymal-like shape. p16 INK4a and IL-8 expression were decreased in cell fraction with higher Vimentin expression. Conclusions Our results suggested the existence of time delay effect in doxorubicin-induced senescence of HeLa cells, and epithelial-mesenchymal transition may resist doxorubicin-induced cell senescence.

show abstract

Section: Discussionmentioning

confidence: 99%

Doxorubicin-Induced Cancer Cell Senescence Shows a Time Delay Effect and Is Inhibited by Epithelial-Mesenchymal Transition (EMT)

Zhang

2019

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…Cisplatin and doxorubicin treatment were performed to induce apoptosis by intrinsic pathway while anti-Fas mAb and TNF-α treatments were carried out to trigger the extrinsic pathway ( Boatright and Salvesen, 2003 ; Morgan et al, 2013 ; Huang et al, 2018 ). In order to attain an apoptosis rate of approximately 50%, drug /ligand concentrations and incubation periods were optimized through dose and time kinetics (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomics Analysis of Circular RNAs Differentially Expressed in Apoptotic HeLa Cells

2019

View full text Add to dashboard Cite

Apoptosis is a form of regulated cell death that plays a critical role in survival and developmental homeostasis. There are numerous reports on regulation of apoptosis by protein-coding genes as well as small non-coding RNAs, such as microRNAs. However, there is no comprehensive investigation of circular RNAs (circRNA) that are differentially expressed under apoptotic conditions. We have performed a transcriptomics study in which we first triggered apoptosis in HeLa cells through treatment with four different agents, namely cisplatin, doxorubicin, TNF-α and anti-Fas mAb. Total RNAs isolated from control as well as treated cells were treated with RNAse R to eliminate the linear RNAs. The remaining RNAs were then subjected to deep-sequencing to identify differentially expressed circRNAs. Interestingly, some of the dys-regulated circRNAs were found to originate from protein-coding genes well-documented to regulate apoptosis. A number of candidate circRNAs were validated with qPCR with or without RNAse R treatment as well. We then took advantage of bioinformatics tools to investigate the coding potential of differentially expressed RNAs. Additionally, we examined the candidate circRNAs for the putative miRNA-binding sites and their putative target mRNAs. Our analyses point to a potential for circRNA-mediated sponging of miRNAs known to regulate apoptosis. In conclusion, this is the first transcriptomics study that provides a complete circRNA profile of apoptotic cells that might shed light onto the potential role of circRNAs in apoptosis.

show abstract

“…LECs treated with different concentrations of curcumin for 48 h were collected and washed with PBS; cell apoptosis and cell cycle were analyzed by flow cytometry (Millipore, Darmstadt, Hesse, Germany) with the MultiCaspase Kit and the Cell Cycle Kit (Millipore, Darmstadt, Hesse, Germany). All procedures were proceeded according to the manufacturer's protocols as we previously did [21,22]. The statistical analysis was performed with the software version 1.3 of the Muse™ Cell Analyzer (Millipore, Darmstadt, Hesse, Germany).…”

Section: Cell Apoptosis and Cell Cycle Analysismentioning

confidence: 99%

Curcumin Inhibits Proliferation and Epithelial‐Mesenchymal Transition in Lens Epithelial Cells through Multiple Pathways

Liu

Mao

Xia

et al. 2020

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Background. Posterior capsule opacification (PCO), a complication of extracapsular lens extraction surgery that causes visual impairment, is characterized by aberrant proliferation and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). Curcumin, exerting inhibitive effects on cell proliferation and EMT in cancer, serves as a possible antidote towards PCO. Methods. Cellular proliferation of LECs after treatment of curcumin was measured with MTT assay and flow cytometry. The transcriptional and expressional levels of proteins related to proliferation and EMT of LECs were quantified by western blotting and real-time PCR. Results. Curcumin was found to suppress the proliferation of LECs by inducing G2/M arrest via possible inhibition of cell cycle-related proteins including CDK1, cyclin B1, and CDC25C. It had also inactivated proliferation pathways involving ERK1/2 and Akt pathways in LECs. On the other hand, curcumin downregulated the EMT of LECs through blocking the TGF-β/Smad pathway and interfering Notch pathway which play important roles in PCO. Conclusions. This study shows that curcumin could suppress the proliferation and EMT in LECs, and it might be a potential therapeutic protection against visual loss induced by PCO.

show abstract

Notch signaling pathway mediates Doxorubicin-driven apoptosis in cancers

Cited by 20 publications

References 31 publications

Doxorubicin-Induced Cancer Cell Senescence Shows a Time Delay Effect and Is Inhibited by Epithelial-Mesenchymal Transition (EMT)

Doxorubicin-Induced Cancer Cell Senescence Shows a Time Delay Effect and Is Inhibited by Epithelial-Mesenchymal Transition (EMT)

Transcriptomics Analysis of Circular RNAs Differentially Expressed in Apoptotic HeLa Cells

Curcumin Inhibits Proliferation and Epithelial‐Mesenchymal Transition in Lens Epithelial Cells through Multiple Pathways

Contact Info

Product

Resources

About