Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Query: UNIPROT:P04637 (
p53
)
77,613
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Natural products are excellent resources for finding lead structures for the development of chemotherapeutic agents. Coumarins are a class of natural compounds found in a variety of plants. In this study, we evaluated the cytotoxic potential of coumarins isolated from Prangos ferulacea (L.) Lindl. in PC3, SKNMC, and H1299 (
p53
null) human carcinoma cell lines. Osthole proved to be an outstanding potent cytotoxic agent especially against PC3 cells. Isoimperatorin exhibited moderate inhibitory effect against SKNMC and PC3 cell lines.
Oxypeucedanin
and braylin did not display any cytotoxic activity. In the next set of experiments, the apoptotic potentials of osthole and isoimperatorin were investigated. Induction of apoptosis by isoimperatorin was accompanied by an increase in activation of caspase-3, -8, and -9 in SKNMC cells and caspase-3 and -9 in PC3 cells. Moreover, isoimperatorin induced apoptosis by upregulating Bax and Smac/DIABLO genes in PC3 and SKNMC cells. Osthole induced apoptosis by downregulating antiapoptotic Bcl-2 in only PC3 cells and upregulating the proapoptotic genes Bax and Smac/DIABLO in PC3, SKNMC, and H1299 cells. The effects of osthole on H1299 cells are important because the loss of
p53
has been associated with poor clinical prognosis in cancer treatment.
...
PMID:Comparative Evaluation of Cytotoxic and Apoptogenic Effects of Several Coumarins on Human Cancer Cell Lines: Osthole Induces Apoptosis in p53-Deficient H1299 Cells. 2527 23
Oxypeucedanin
(
OPD
), a furocoumarin compound from
Angelica dahurica
(Umbelliferae), exhibits potential antiproliferative activities in human cancer cells. However, the underlying molecular mechanisms of
OPD
as an anticancer agent in human hepatocellular cancer cells have not been fully elucidated. Therefore, the present study investigated the antiproliferative effect of
OPD
in SK-Hep-1 human hepatoma cells.
OPD
effectively inhibited the growth of SK-Hep-1 cells. Flow cytometric analysis revealed that
OPD
was able to induce G
2
/M phase cell cycle arrest in cells. The G
2
/M phase cell cycle arrest by
OPD
was associated with the downregulation of the checkpoint proteins cyclin B1, cyclin E, cdc2, and cdc25c, and the up-regulation of p-chk1 (Ser345) expression. The growth-inhibitory activity of
OPD
against hepatoma cells was found to be
p53
-dependent. The
p53
-expressing cells (SK-Hep-1 and HepG2) were sensitive, but
p53
-null cells (Hep3B) were insensitive to the antiproliferative activity of
OPD
.
OPD
also activated the expression of
p53
, and thus leading to the induction of MDM2 and p21, which indicates that the antiproliferative activity of
OPD
is in part correlated with the modulation of
p53
in cancer cells. In addition, the combination of
OPD
with gemcitabine showed synergistic growth-inhibitory activity in SK-Hep-1 cells. These findings suggest that the anti-proliferative activity of
OPD
may be highly associated with the induction of G
2
/M phase cell cycle arrest and upregulation of the
p53
/MDM2/p21 axis in SK-HEP-1 hepatoma cells.
...
PMID:The Antiproliferative Activity of Oxypeucedanin via Induction of G
2
/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells. 3197 61
