Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.62 (
caspase-9
)
7,507
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In the course of our screening for novel modulators on cell cycle progression and apoptosis as anticancer drug candidates, we generated an analogue of sangivamycin,
MCS
-C2, designated as 4-amino-6-bromo-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. This study was aimed to evaluate the molecular mechanisms on cell cycle arrest and apoptotic induction of
MCS
-C2 in human lung cancer A549 cells. To investigate the effects of
MCS
-C2 on cell cycle progression in A549 cells, we measured DNA content of A549 cells treated with 5 microM of HY253 using flow cytometric analysis. The flow cytometric analysis revealed an appreciable G(2) phase arrest in A549 cells treated with 5 micronM of
MCS
-C2. This
MCS
-C2-induced G(2) phase arrest is associated with significant up-regulation of p53 and p21(Cip1) in A549 cells. Furthermore, TUNEL assay was used to examine apoptotic induction in A549 cells treated with 5 microM of
MCS
-C2 for 48 h. In addition, the effects of
MCS
-C2 on apoptosis-associated proteins in A549 cells were examined using Western blot analysis. The apoptotic induction in
MCS
-C2-treated A549 cells is associated with cytochrome c release from mitochondria which in turn resulted in the activation of
caspase-9
and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). In conclusion, based on these results, we suggest that
MCS
-C2 may be a potent cancer chemotherapeutic candidate for use in treating human lung cancer cells via up-regulation and activation of p53.
...
PMID:Cell cycle arrest and cytochrome c-mediated apoptotic induction in human lung cancer A549 cells by MCS-C2, an analogue of sangivamycin. 2020 52
