Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells

Chen, Wei; Li, Ping; Liu, Yi; Yu, Yang; Ye, Xueting; Zhang, Fangyi; Huang, Hang

doi:10.1186/s13046-018-0987-9

Cited by 65 publications

(49 citation statements)

References 33 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Severe ER stress has the ability to initiate another atypical intrinsic apoptosis response [ 200 ]. Induction of ER stress activation and PCa cell apoptosis by both Chelerythrine (CHE) and Isoalantolactone (IALT) is dependent on ROS generation [ 193 , 201 ]. Mechanically, IALT increases the levels of ROS-dependent p-eIF2 α and ATF4 in the PC-3 and DU145 cells, thus stimulating expression of the transcription factor CHOP that inhibits the expression of Bcl-2 and is strictly responsible for the initiation of the cell apoptosis cascade [ 201 – 203 ].…”

Section: Roles Of Ros Molecules In Pcamentioning

confidence: 99%

“…Induction of ER stress activation and PCa cell apoptosis by both Chelerythrine (CHE) and Isoalantolactone (IALT) is dependent on ROS generation [ 193 , 201 ]. Mechanically, IALT increases the levels of ROS-dependent p-eIF2 α and ATF4 in the PC-3 and DU145 cells, thus stimulating expression of the transcription factor CHOP that inhibits the expression of Bcl-2 and is strictly responsible for the initiation of the cell apoptosis cascade [ 201 – 203 ]. Mitochondrial outer membrane permeabilization (MOMP) also results in elevated cytoplasmic proapoptotic molecules containing apoptosis-inducing factor (AIF) and endonuclease G (Endo G) in response to organelle damage induced by ROS, and these molecules function in a caspase-independent manner [ 204 ].…”

Section: Roles Of Ros Molecules In Pcamentioning

confidence: 99%

See 1 more Smart Citation

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

Han

Wang

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by-product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.

show abstract

Section: Roles Of Ros Molecules In Pcamentioning

confidence: 99%

Section: Roles Of Ros Molecules In Pcamentioning

confidence: 99%

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

Han

Wang

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Promote its transcription [30]. The results showed that the STAT3 phosphorylation was decreased, indicating that PN can block the phosphorylation of STAT3, thereby preventing its entry into the nucleus.…”

Section: Discussionmentioning

confidence: 93%

Anti-Tumor Effect and Mechanism of Parthenolide in Gastric Cancer Cellline BGC-823

Zhu¹,

Zhang²,

Guo³

et al. 2019

OALib

View full text Add to dashboard Cite

Objective: To study the anti-tumor effect and mechanism of parthenolide in gastric cancer cell BGC-823. Methods: The cck8 assay was used to detect the changes of BGC-823 cells viability after treatment with different concentrations of parthenolide at different time points. The proliferation ability of BGC-823 cells was detected by clone formation assay. And the cell cycle and apoptosis were measured by flow cytometry. Meanwhile, to detect the difference in intracellular ROS production levels, the fluorescence assay was used. And with the help of western blotting, cell cycle-and apoptosis-related protein expression can be detected. Results: Parthenolide could inhibit the viability of BGC-823 cells in a dose-and time-dependent manner (P < 0.01). In BGC-823 cells exposed to parthenolide, the apoptosis rate was found significantly increased (P < 0.01), and the protein expression of cleaved-caspase3, cleaved-caspase8, and cleaved-caspase9 significantly increased (P < 0.01); the cell cycle was arrested at G1phase (P < 0.01); the protein levels of CyclinD1 and CyclinE1 decreased (P < 0.01), and the expression of P53 and P21 protein increased (P < 0.01); massive intracellular ROS generation was found (P < 0.01). Furthermore, the nuclear protein levels of c-Myc, E2F1, and NF-κB and the protein level of phosphorylated STAT3 decreased in BGC-823 cells exposed to parthenolide (P < 0.01). Conclusion: Parthenolide may inhibit the proliferation of BGC-823 cells and induce G1-phase cell cycle arrest and apoptosis via inhibiting STAT3-c-Myc-E2F1 axis.

show abstract

“…Celastrol, which contains a reactive quinone methide moiety enabling covalent attachment to cysteine residues (49), including direct binding and inhibition of c-Myc-Max heterodimers (50), cancerous inhibitor of protein phosphatase 2A (CIP2A) (51), STAT3 (52), SHOC-2 to inhibit ERK signaling (53), IKKα and IKKβ (54), and HSP90-chaperone interactions (55-57); directly binds nearly 70 protein targets in a proteome microarray assay (53); and affects other cellular signaling pathways including protein phosphatase 2A-Akt, AMPK, and WNT/β-catenin (58). Isoalantolactone activates AMPKα (28) and inhibits STAT3 (59) and IKKβ (60). Camptothecin inhibits topoisomerase I (61).…”

Section: Discussionmentioning

confidence: 99%

Assessment of NR4A Ligands that Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1

Munoz-Tello

Lin

Khan

et al. 2020

Preprint

View full text Add to dashboard Cite

Nurr1/NR4A2 is an orphan nuclear receptor transcription factor implicated as a potential drug target for neurological disorders including Alzheimer’s and Parkinson’s diseases. Previous studies identified small molecule modulators of NR4A nuclear receptors including Nurr1 and Nur77/NR4A1; it remains unclear whether these ligands affect Nurr1 through direct binding or indirect non-binding mechanisms. We assessed a panel of twelve ligands reported to affect NR4A activity for Nurr1-dependent and Nurr1-independent transcriptional effects and binding to the Nurr1 ligand-binding domain (LBD). Most of the NR4A ligands show Nurr1-independent effects on transcription in a cell type-specific manner, suggesting they may function through binding to effector proteins whose downstream activities influence Nurr1 function. Protein NMR spectroscopy structural footprinting data show that 4-amino-7-chloroquinoline derivatives (amodiaquine and chloroquine) and cytosporone B directly bind the Nurr1 LBD. In contrast, other NR4A ligands including commercially available compounds such as C-DIM12, celastrol, camptothecin, IP7e, isoalantolactone, and TMPA do not bind the Nurr1 LBD. Interestingly, previous crystal structures indicate that cytosporone B analogs bind to surface pockets in the Nur77 LBD, but protein NMR data indicate cytosporone B likely binds to the Nurr1 orthosteric pocket. These findings should influence medicinal chemistry efforts that desire to optimize Nurr1-binding ligands as opposed to ligands that function through binding to Nurr1 effector proteins.

show abstract

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells

Cited by 65 publications

References 33 publications

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

Anti-Tumor Effect and Mechanism of Parthenolide in Gastric Cancer Cellline BGC-823

Assessment of NR4A Ligands that Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1

Contact Info

Product

Resources

About