The molecular mechanism of apoptosis upon caspase-8 activation: Quantitative experimental validation of a mathematical model

Kominami, Katsuya; Nakabayashi, Jun; Nagai, Takeharu; Tsujimura, Yasuhiro; Chiba, Kumiko; Kimura, Haruna; Miyawaki, Atsushi; Sawasaki, Tatsuya; Yokota, Hideo; Manabe, Noboru; Sakamaki, Kazuhiro

doi:10.1016/j.bbamcr.2012.07.003

Cited by 54 publications

(46 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The intrinsic and extrinsic pathways converge at caspase-3. Active caspases and 8 of the intrinsic and extrinsic pathways, respectively, have been shown to directly cleave and activate the effector protease caspase-3 (Kominami et al, 2012). In the present study, we have shown that caspases-3 and -7 are activated during BtxAmediated apoptosis.…”

Section: Discussionsupporting

confidence: 59%

Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line

Bandala

Pérez-Santos²,

Lara‐Padilla³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

The present study was performed to assess the activity of the botulinum toxin A on breast cancer cells. The T47D cell line was exposed to diverse concentrations of the botulinum toxin A and cell viability and apoptosis were estimated using MTT and propidium iodine/annexin V methods, respectively. Botulinum toxin A exerted greater cytotoxic activity in T47D cells in comparison with MCF10A normal cells; this appeared to be via apoptotic processes caspase-3 and -7. In conclusion, botulinum toxin A induces caspase-3 and -7 dependent apoptotic processes in the T47D breast cancer cell line.

show abstract

Section: Discussionsupporting

confidence: 59%

Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line

Bandala

Pérez-Santos²,

Lara‐Padilla³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…11,28 Additionally, there is a higher concentration of initiator caspases versus executioner caspases in apoptotic cells. 29 Thus, excess concentrations of initiator caspases were used to ensure caspase-3 selectivity.…”

Section: Resultsmentioning

confidence: 99%

Sensitive and Selective Plasmon Ruler Nanosensors for Monitoring the Apoptotic Drug Response in Leukemia

et al. 2014

View full text Add to dashboard Cite

Caspases are proteases involved in cell death, where caspase-3 is the chief executioner that produces an irreversible cutting event in downstream protein substrates and whose activity is desired in the management of cancer. To determine such activity in clinically relevant samples with high signal-to-noise, plasmon rulers are ideal because they are sensitively affected by their interparticle separation without ambiguity from photobleaching or blinking effects. A plasmon ruler is a noble metal nanoparticle pair, tethered in close proximity to one another via a biomolecule, that acts through dipole–dipole interactions and results in the light scattering to increase exponentially. In contrast, a sharp decrease in intensity is observed when the pair is confronted by a large interparticle distance. To align the mechanism of protease activity with building a sensor that can report a binary signal in the presence or absence of caspase-3, we present a caspase-3 selective plasmon ruler (C3SPR) composed of a pair of Zn0.4Fe2.6O4@SiO2@Au core–shell nanoparticles connected by a caspase-3 cleavage sequence. The dielectric core (Zn0.4Fe2.6O4@SiO2)-shell (Au) geometry provided a brighter scattering intensity versus solid Au nanoparticles, and the magnetic core additionally acted as a purification handle during the plasmon ruler assembly. By monitoring the decrease in light scattering intensity per plasmon ruler, we detected caspase-3 activity at single molecule resolution across a broad dynamic range. This was observed to be as low as 100 fM of recombinant material or 10 ng of total protein from cellular lysate. By thorough analyses of single molecule trajectories, we show caspase-3 activation in a drug-treated chronic myeloid leukemia (K562) cancer system as early as 4 and 8 h with greater sensitivity (2- and 4-fold, respectively) than conventional reagents. This study provides future implications for monitoring caspase-3 as a biomarker and efficacy of drugs.

show abstract

“…Caspase-8 proteolytically processes a downstream effector caspase-3 [99]. Once caspase-8 is activated, its downstream effector is channelized through receptors and termed as an extrinsic pathway [100]. However, intrinsic pathway is functionalized through entry of truncated Bid (tBid) into mitochondrion.…”

Section: Oleanolic Acid As Anticancer Agentmentioning

confidence: 99%

Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

Žiberna

Šamec

Mocan

et al. 2017

IJMS

116

View full text Add to dashboard Cite

Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5 adenosine monophosphate-activated protein kinase, extracellular signal-regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical.

show abstract

The molecular mechanism of apoptosis upon caspase-8 activation: Quantitative experimental validation of a mathematical model

Cited by 54 publications

References 87 publications

Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line

Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line

Sensitive and Selective Plasmon Ruler Nanosensors for Monitoring the Apoptotic Drug Response in Leukemia

Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

Contact Info

Product

Resources

About