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: UMLS:C0009402 (
colorectal cancer
)
53,228
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ohmyungsamycin A (
1
), a novel cyclic peptide discovered from a marine
Streptomyces
sp., was previously reported with antibacterial and anticancer activities. However, the antitumor activities and the underlying molecular mechanisms of
1
remain to be elucidated. Compound
1
inhibited the proliferation and tumor growth of HCT116 human
colorectal cancer
cells based on both
in vitro
cell cultures and an
in vivo
animal model. A cDNA microarray analysis revealed that
1
downregulated genes involved in cell cycle checkpoint control. Compound
1
also induced G
0
/G
1
cell cycle arrest that was mediated by the regulation of S-phase kinase-associated protein 2 (Skp2)-p27 axis and
minichromosome maintenance protein 4
(
MCM4
). Furthermore, a longer exposure of
1
exhibited an accumulation of a sub-G
1
phase cell population, which is characteristic of apoptotic cells. The induction of apoptosis by
1
was also associated with the modulation of caspase family proteins. Compound
1
effectively suppressed tumor growth in a xenograft mouse model subcutaneously implanted with HCT116 cells. In addition, analysis of tumors revealed that
1
upregulated the expression of the CDK inhibitor p27 but downregulated the expression of Skp2 and
MCM4
. These findings demonstrate the involvement of
1
in cell cycle regulation and the induction of apoptosis in human
colorectal cancer
cells.
...
PMID:Antitumor Activity of Ohmyungsamycin A through the Regulation of the Skp2-p27 Axis and MCM4 in Human Colorectal Cancer Cells. 3189 83
