Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microtubule-associated protein 1A/1B-light chain 3 (LC3)-II is essential for autophagosome formation and is widely used to monitor autophagic activity. We show that CGK733 induces LC3 II and LC3-puncta accumulation, which are not involved in the activation of autophagy. The treatment of CGK733 did not alter the autophagic flux and was unrelated to p62 degradation. Treatment with CGK733 activated the AMP-activated protein kinase (AMPK) and protein kinase RNA-like endoplasmic reticulum kinase/CCAAT-enhancer-binding protein homologous protein (PERK/CHOP) pathways and elevated the expression of p21Waf1/Cip1. Inhibition of both AMPK and PERK/CHOP pathways by siRNA or chemical inhibitor could block CGK733-induced p21Waf1/Cip1 expression as well as caspase-3 cleavage. Knockdown of LC3 B (but not LC3 A) abolished CGK733-triggered LC3 II accumulation and consequently diminished AMPK and PERK/CHOP activity as well as p21Waf1/Cip1 expression. Our results demonstrate that CGK733-triggered LC3 II formation is an initial event upstream of the AMPK and PERK/CHOP pathways, both of which control p21Waf1/Cip1 expression.
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PMID:CGK733-induced LC3 II formation is positively associated with the expression of cyclin-dependent kinase inhibitor p21Waf1/Cip1 through modulation of the AMPK and PERK/CHOP signaling pathways. 2648 79

The aim of the present study was to explore sunitinib-induced autophagic effects and the specific molecular mechanisms involved, in vitro, using PC-3 and LNCaP human prostate cancer cell lines. Cells were exposed to escalating doses of sunitinib treatment and subsequent cell viability and cell cycle analyses were performed to evaluate the inhibitory effect of sunitinib in vitro. Immunofluorescence staining of microtubule associated protein 1A/1B-light chain 3 (LC3) puncta was employed to assess autophagy levels after sunitinib treatment. Western blot analysis was performed to evaluate variations in the levels of LC3, sequestosome-1, extracellular signal regulated kinase 1/2 (ERK1/2), mammalian target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K) and cleaved caspase-3 proteins. The present study revealed that sunitinib treatment inhibited cell growth and triggered autophagy in a dose-dependent manner in both cell lines. In addition, sunitinib activated ERK1/2 and inhibited mTOR/p70S6K signaling. Sunitinib-induced autophagy was notably reversed by ERK1/2 kinase inhibitor, U0126. Furthermore, inhibition of sunitinib-induced autophagy by 3-methyladenine enhanced apoptosis and exhibited improved cell viability, which indicated that sunitinib induces not only apoptosis but also autophagic cell death in prostate cancer cell lines. These results may lead to an improved understanding of the mechanism of sunitinib's cytotoxic action and may provide evidence that combined sunitinib autophagy-regulating treatment may be of benefit to anti-prostate cancer therapy.
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PMID:Antitumor effect of sunitinib in human prostate cancer cells functions via autophagy. 2841 68