Fluopsin C induces oncosis of human breast adenocarcinoma cells

Ma, Liang; Jiang, Chuanhai; Cui, Min; Lü, Rong; Liu, Shanshan; Zheng, Bingbing; Li, Lin; Li, Xia

doi:10.1038/aps.2013.44

Cited by 26 publications

(20 citation statements)

References 27 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These characteristics of cell death induced by NADA are consistent with typical features of cell death termed oncosis (36,39,40). Like other cases of oncosis (41), cleavage of caspase-3 can be detected in NADA-treated Ba/F3-N cells (Supplementary Fig.…”

Section: Lead Compound Identificationsupporting

confidence: 83%

N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation

Huang

Zhang

et al. 2017

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block RAS oncogenic signaling by a distinct mechanism. Because the biological activity of RAS proteins relies upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS-specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors. Further analyses show that NADA is more active in inhibiting the NRAS transformation and signaling than that of KRAS4B. Mechanistically, NADA blocks the plasma membrane translocation of NRAS, but not that of KRAS4B. In addition, NADA inhibits plasma membrane translocation and neoplastic transformation of oncogenic KRAS4A. Interestingly, NADA also redistributes the cytoplasmic NRAS to the Golgi apparatus in a palmitoylation-dependent manner. The results indicate that NADA inhibits NRAS and KRAS4A plasma membrane translocation by targeting a novel molecular process. The new findings would help to develop novel targeted therapies for a broad range of human cancers.

show abstract

Section: Lead Compound Identificationsupporting

confidence: 83%

N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation

Huang

Zhang

et al. 2017

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…As is known, oncosis is characterized by loss of volume control with massive swelling of most intracellular compartment, often based on ATP deficiency but also related to direct damage to the plasma membrane. It could be quantitated by flow cytometry with PI staining and LDH leakage [6,15,26,27] . Combined with the above result of LDH leakage ( fig.…”

Section: Discussionmentioning

confidence: 99%

Intervention timing and effect of PJ34 on astrocytes during oxygen-glucose deprivation/reperfusion and cell death pathways

Cai

Zhang

Huang

et al. 2015

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

View full text Add to dashboard Cite

Poly (ADP-ribose) polymerase-1 (PARP-1) plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relationship with intervention timing. During ischemia injury, apoptosis and oncosis are the two main cell death pathway sin the ischemic core. The participation of astrocytes in ischemia-reperfusion induced cell death has triggered more and more attention. Here, we examined the protective effects and intervention timing of the PARP-1 inhibitor PJ34, by using a mixed oxygen-glucose deprivation/reperfusion (OGDR) model of primary rat astrocytes in vitro, which could mimic the ischemia-reperfusion damage in the "ischemic core". Meanwhile, cell death pathways of various PJ34 treated astrocytes were also investigated. Our results showed that PJ34 incubation (10 μmol/L) did not affect release of lactate dehydrogenase (LDH) from astrocytes and cell viability or survival 1 h after OGDR. Interestingly, after 3 or 5 h OGDR, PJ34 significantly reduced LDH release and percentage of PI-positive cells and increased cell viability, and simultaneously increased the caspase-dependent apoptotic rate. The intervention timing study demonstrated that an earlier and longer PJ34 intervention during reperfusion was associated with more apparent protective effects. In conclusion, earlier and longer PJ34 intervention provides remarkable protective effects for astrocytes in the "ischaemic core" mainly by reducing oncosis of the astrocytes, especially following serious OGDR damage.

show abstract

“…Ma et al [25] focused on an antibiotic isolated from Pseudomonas jinjuensis , which was previously proved to have anticancer potential, and found that this antibiotic could induce oncosis in breast cancer cells. Steroidal alkaloidal saponins were demonstrated to be natural anticancer agents as they induced apoptosis in cancer cells [26].…”

Section: Discussionmentioning

confidence: 99%

Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

Guang

Jiang

Wang

et al. 2014

BioMed Research International

View full text Add to dashboard Cite

Aim. Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid. Methods. MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Δψm). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain. Results. Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death. The oncotic related protein calpain was found to increase time-dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity. Conclusions. Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells.

show abstract

Fluopsin C induces oncosis of human breast adenocarcinoma cells

Cited by 26 publications

References 27 publications

N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation

N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation

Intervention timing and effect of PJ34 on astrocytes during oxygen-glucose deprivation/reperfusion and cell death pathways

Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

Contact Info

Product

Resources

About