Caspase-8 is well-characterized to initiate an apoptotic pathway triggered by the external stimuli. The proximity-driven model recently has been proposed to interpret the activation mechanism of caspase-8 in so-far unprecedent detail, in which dimerization, autocleavage, and inhibitor of caspase-8 are indispensable. Intriguingly, death effector domains (DEDs) and ubiquitination after active caspase-8 is released into cytosol can also promote cell apoptosis indirectly. In addition to the proapoptotic role of caspase-8, there is emerging evidence to indicate that the precursor of caspase-8, procaspase-8, has an important function in cell adhesion and migration. Phosphorylation of caspase-8 by c-src controls these functions by preventing the conversion of procaspase-8 to caspase-8. This provides a mechanism to switch these opposing functions. In the migratory role, procaspase-8 interacts with the phosphatidylinositol-3-OH kinase (PI3K) regulatory subunit p85alpha and c-src to modulate signaling by Rac and extracellular signal-regulated kinase (ERK) 1/2, and promotes calpain2 activation. Here, the focus of this review is to highlight three respective aspects of caspase-8, including precursor functions, activation mechanism and maintenance of activity.
Crocin is a carotenoid of the saffron extract that exhibits antitumor activity against many human tumors. However, the effects of crocin on HL-60 cells in vivo have not been evaluated. This study aimed to examine the effects of crocin on HL-60 cells in vitro and in vivo and investigate the underlying mechanisms. HL-60 cells were treated by crocin, and cell proliferation, apoptosis, and cell cycle profiles were examined by MTT assay, AO/EB staining, and flow cytometry, respectively. Furthermore, HL-60 cells were xenografted into nude mice and treated by crocin, the tumor weight and size were calculated, and the expression of Bcl-2 and Bax in xenografts was detected by immunohistochemical staining. The results showed that crocin (0.625–5 mg/mL) inhibited HL-60 cell proliferation and induced apoptosis and cell cycle arrest at G0/G1 phase, in a concentration and time-dependent manner. In addition, crocin (6.25, 25 mg/kg) inhibited the tumor weight and size of HL-60 xenografts in nude mice, inhibited Bcl-2 expression, and increased Bax expression in xenografts. In summary, crocin inhibits the proliferation and tumorigenicity of HL-60 cells, which may be mediated by the induction of apoptosis and cell cycle arrest and the regulation of Bcl-2 and Bax expression.
In patients with operable esophageal squamous cell carcinoma, perioperative regimen of PCF can significantly improve 5-year relapse-free and overall survival comparing with preoperative chemotherapy alone. (The trial has been registered at ClinicalTrials.gov, number NCT01225523.).
These findings indicate that a standardized 5-year surveillance period is inadequate for some cancers while excessive for others. High-risk cancers require the most resources with the longest high-risk period, highest persistent baseline mortality risk, and longest period of primary cancer mortality, all arguing for longer follow-up with an oncologist in these cancers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.