|Biol Pharm Bull. 2006 Aug;29(8):1639-44. |
|The course of uncarinic acid E-induced apoptosis of HepG2 cells from damage to DNA and p53 activation to mitochondrial release of cytochrome c.[Pubmed: 16880619]|
|Uncarinic acid E, an active component isolated from Gelsemium elegans BENTH, has been reported to exhibit antitumor effects, but little is known about its molecular mechanisms of action.|
METHODS AND RESULTS:
In this study, the growth-inhibitory activity of Uncarinic acid E for HepG2 cells is in time- and dose-dependent manner. HepG2 cells treated with Uncarinic acid E exhibited several typical characteristics of apoptosis through photomicroscopical observation, DNA agarose gel electrophoresis. The inhibitory effect of Uncarinic acid E on HepG2 cells was partially reversed by the inhibitors of pan-caspase, caspase-3 and caspase-6. The protein expression ratio of Bcl-xL/Bax and Bcl-2/Bax was down-regulated and Uncarinic acid E-induced apoptosis involves the initial phase mediated by the balance among Bcl-xL, Bcl-2 and Bax proteins, resulting in cytochrome c release from the mitochondria. Uncarinic acid E significantly increased the expression of p53 proteins indicates that p53 plays a pivotal role in the initiation phase of Uncarinic acid E-induced HepG2 cell apoptosis. The phoshatidylinositol 3-kinase (PI3-K) family inhibitor wortmanin and the MEK inhibitor (PD98059) rescued the viability loss induced by Uncarinic acid E through the expression of p53.
Taken together, Uncarinic acid E induces apoptosis in HepG2 cells via accumulation of p53, alters the Bax/Bcl-2 ratio, and activates caspases, resulting in cytochrome c release from the mitochondria.
|Chem Biodivers. 2017 Apr;14(4). |
|Cytotoxic Triterpenoids from the Barks of Betula platyphylla var. japonica.[Pubmed: 28052515 ]|
METHODS AND RESULTS:
Phytochemical investigation on the barks of Betula platyphylla var. japonica (Betulaceae) was carried out, resulting in the isolation and identification of three new triterpenoids, 27-O-cis-caffeoylcylicodiscic acid (1), 27-O-cis-feruloylcylicodiscic acid (2), and 27-O-cis-caffeoylmyricerol (3), along with six known triterpenoids, obtusilinin (4), winchic acid (5), 27-O-trans-caffeoylcylicodiscic acid (6), Uncarinic acid E (7), myriceric acid B (8), and 3-O-trans-caffeoyloleanolic acid (9). The structures of the new compounds were elucidated by extensive spectroscopic methods, including 1D- and 2D-NMR, and HR-ESI-MS. All of the isolated compounds were evaluated for cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and Bt549).
Compounds 2, 6, 8, and 9 exhibited potent cytotoxicity against all of the tumor cells tested (IC50 < 10.0 μm), while compounds 3, 4, 5, and 7 showed moderate cytotoxicity against all of the tumor cells tested (IC50 < 20.0 μm).