MLKL contributes to shikonin-induced glioma cell necroptosis via promotion of chromatinolysis

Ding, Ye; He, Chuan; Lu, Shan; Wang, Xuanzhong; Wang, Chongcheng; Wang, Lei; Zhang, Ji; Piao, Meihua; Chi, Guangfan; Luo, Yan; Sai, Ke; Ge, Pengfei

doi:10.1016/j.canlet.2019.09.007

Cited by 44 publications

(32 citation statements)

References 39 publications

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“…To further confirm cell death induction, we evaluated γ-H2AX labeling in cells treated for 48 h with either 250 µM ATP or adenosine ( Figure 4 C). Beside its canonical function in the DNA damage response processes, Ser-139 phosphorylation of the histone variant H2AX is indeed involved in both apoptosis and caspase-independent programmed necrosis (necroptosis) [ 57 , 58 , 59 ]. Importantly, γ-H2AX labeling showed very similar patterns to those seen for Annexin V/PI, suggesting that cell death induced by extracellular ATP implies DNA damage in HT29, HCT116 and LS174T cells.…”

Section: Resultsmentioning

confidence: 99%

Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine

Dillard

Borde

Mohammad

et al. 2021

IJMS

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The purine nucleotide adenosine triphosphate (ATP) is known for its fundamental role in cellular bioenergetics. However, in the last decades, different works have described emerging functions for ATP, such as that of a danger signaling molecule acting in the extracellular space on both tumor and stromal compartments. Beside its role in immune cell signaling, several studies have shown that high concentrations of extracellular ATP can directly or indirectly act on cancer cells. Accordingly, it has been reported that purinergic receptors are widely expressed in tumor cells. However, their expression pattern is often associated with contradictory cellular outcomes. In this work, we first investigated gene expression profiles through “RNA-Sequencing” (RNA Seq) technology in four colorectal cancer (CRC) cell lines (HT29, LS513, LS174T, HCT116). Our results demonstrate that CRC cells mostly express the A2B, P2X4, P2Y1, P2Y2 and P2Y11 purinergic receptors. Among these, the P2Y1 and P2Y2 coding genes are markedly overexpressed in all CRC cells compared to the HCEC-1CT normal-like colonic cells. We then explored the cellular outcomes induced by extracellular ATP and adenosine. Our results show that in terms of cell death induction extracellular ATP is consistently more active than adenosine against CRC, while neither compound affected normal-like colonic cell survival. Intriguingly, while for the P2Y2 receptor pharmacological inhibition completely abolished the rise in cytoplasmic Ca2+ observed after ATP exposure in all CRC cell lines, Ca2+ mobilization only impacted the cellular outcome for HT29. In contrast, non-selective phosphodiesterase inhibition completely abolished the effects of extracellular ATP on CRC cells, suggesting that cAMP and/or cGMP levels might determine cellular outcome. Altogether, our study provides novel insights into the characterization of purinergic signaling in CRC.

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Section: Resultsmentioning

confidence: 99%

Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine

Dillard

Borde

Mohammad

et al. 2021

IJMS

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“…Thus, mitochondria damage is prior to its removal by autophagy. It has been demonstrated that apoptosis, necroptosis, and parthanatos contributed to cell death via causing mitochondrial damage and nuclear translocation of AIF [38][39][40] , but it remains elusive whether autophagy plays a role in impairing mitochondria and promoting AIF translocation from mitochondria to nuclei. In this study, we found that blocking autophagy with 3MA, bafilomycin A1 or by knocking down ATG5 with SiRNA not only inhibited silibinin-induced glioma cell death, but also prevented mitochondrial accumulation of superoxide and nuclear Silibinin inhibits glycolysis in glioma cells, which results in autophagy activation.…”

Section: Discussionmentioning

confidence: 99%

Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF

Wang

et al. 2020

Cell Death Dis

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Induction of lethal autophagy has become a strategy to eliminate glioma cells, but it remains elusive whether autophagy contributes to cell death via causing mitochondria damage and nuclear translocation of apoptosis inducing factor (AIF). In this study, we find that silibinin induces AIF translocation from mitochondria to nuclei in glioma cells in vitro and in vivo, which is accompanied with autophagy activation. In vitro studies reveal that blocking autophagy with 3MA, bafilomycin A1 or by knocking down ATG5 with SiRNA inhibits silibinin-induced mitochondrial accumulation of superoxide, AIF translocation from mitochondria to nuclei and glioma cell death. Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis. Then, autophagy improves intracellular H 2 O 2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT. The increased H 2 O 2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria. Knockdown of BNIP3 with SiRNA inhibits silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide, and AIF translocation from mitochondria to nuclei, as well as prevents glioma cell death. Furthermore, we find that the improved H 2 O 2 reinforces silibinin-induced glycolysis dysfunction. Collectively, autophagy contributes to silibinininduced glioma cell death via promotion of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF.

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“…Likewise, the formation of biofilms brings great challenges to the elimination of S. aureus . Shikonin is a natural naphthoquinone compound extracted from comfrey root, and some current clinical animal experiments have proven that it has anti-inflammatory, anti-tumor and extensive antibacterial activities [ 29 , 30 , 31 ]. However, its antibacterial effect on foodborne S. aureus is rarely studied.…”

Section: Discussionmentioning

confidence: 99%

Control of Foodborne Staphylococcus aureus by Shikonin, a Natural Extract

Wan¹,

Wang²,

Zhang³

et al. 2021

Foods

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Foodborne Staphylococcus aureus (S. aureus) has attracted widespread attention due to its foodborne infection and food poisoning in human. Shikonin exhibits antibacterial activity against a variety of microorganisms, but there are few studies on its antibacterial activity against S. aureus. This study aims to explore the antibacterial activity and mechanism of shikonin against foodborne S. aureus. The results show that the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of shikonin were equal for all tested strains ranging from 35 μg/mL to 70 μg/mL. Shikonin inhibited the growth of S. aureus by reducing intracellular ATP concentrations, hyperpolarizing cell membrane, destroying the integrity of cell membrane, and changing cell morphology. At the non-inhibitory concentrations (NICs), shikonin significantly inhibited biofilm formation of S. aureus, which was attributed to inhibiting the expression of cidA and sarA genes. Moreover, shikonin also markedly inhibited the transcription and expression of virulence genes (sea and hla) in S. aureus. In addition, shikonin has exhibited antibacterial ability against both planktonic and biofilm forms of S. aureus. Importantly, in vivo results show that shikonin has excellent biocompatibility. Moreover, both the heat stability of shikonin and the antimicrobial activity of shikonin against S. aureus were excellent in food. Our findings suggest that shikonin are promising for use as a natural food additive, and it also has great potential in effectively controlling the contamination of S. aureus in food and reducing the number of illnesses associated with S. aureus.

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MLKL contributes to shikonin-induced glioma cell necroptosis via promotion of chromatinolysis

Cited by 44 publications

References 39 publications

Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine

Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine

Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF

Control of Foodborne Staphylococcus aureus by Shikonin, a Natural Extract

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