[Show abstract][Hide abstract]ABSTRACT: Gastric cancer is one of the most common malignancies worldwide, and the main cause of cancer-related death in Asia. The present study assessed the anticancer effects of euphol, a triterpene alcohol with anti-inflammatory and antiviral activities on human gastric cancer cells. Euphol showed higher cytotoxicity activity against human gastric CS12 cancer cells than against noncancer CSN cells. In addition, it up-regulated the pro-apoptotic protein BAX and down-regulated the prosurvival protein Bcl-2, causing mitochondrial dysfunction, possibly by caspase-3 activation. The anti-proliferative effects of euphol were associated with the increased p27(kip1) levels and decreased cyclin B1 levels. Inhibition of ERK1/2 activation by PD98059 reversed euphol-induced pro-apoptotic protein expression and cell death. Taken together, these findings suggest that euphol selectively induced gastric cancer cells apoptosis by modulation of ERK signaling, and could thus be of value for cancer therapy.
No preview · Article · May 2012 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
[Show abstract][Hide abstract]ABSTRACT: Pregnenolone (1) was used as a template to develop new anticancer compounds. Ring-D modification of 1 resulted in the synthesis of benzylidenes 2-17, pyrazolines 18-76, pyrazoles 85-91, hydrazones 77-84, and oximes 92-107 derivatives. The structure of compound 107 was also deduced through single crystal X-ray diffraction studies. The inclusion of furanyl and pyridyl rings to pregnenolone skeleton increases the cytotoxicity of all compounds significantly. Among benzylidene derivatives, only heterocyclic enone 8 (IC50=0.74 μM/mL against HepG2), and 17 (IC50=4.49 μM/mL against HepG2, IC50=5.01 μM/mL against MDA-MB-230 cancer cell line) exhibited a significant activity. The cytotoxicity data of pyrazoline derivatives 18-76 revealed that only furanyl bearing pyrazolines 40, 42-44, 48, and 49 exhibited significant activities. While all (O-carboxymethyl) oximes, hydazones, and pyrazoles derivatives of pregnenolone did not show any significant activity against both the cell lines. Thus the furanyl bearing enone 8 (IC50=0.74 μM/mL against HepG2), and its pyrazoline derivative 48 (IC50=0.91 μM/mL against MDA-MB-230 cancer cell lines) were identified as the most active compounds in all derivatives of pregnenolone.
[Show abstract][Hide abstract]ABSTRACT: The protoapigenone analogue WYC02-9, a novel synthetic flavonoid, has been shown to act against a variety of experimental tumors. However, its effects on prostate cancer and its mechanism of action are unknown. Thus, WYC02-9 was investigated for its cytotoxicity against DU145 prostate cancer cells, as was the underlying mechanisms by which WYC02-9 might induce DNA damage and apoptotic cell death through reactive oxygen species (ROS). WYC02-9 inhibited the cell growth of three prostate cancer cell lines, especially DU145 cells. In DU145 cells, WYC02-9 increased the generation of intracellular ROS, followed by induction of DNA damage and activation of the ATM-p53-H2A.X pathway and checkpoint-related signals Chk1/Chk2, which led to increased numbers of cells in the S and G2/M phases of the cell cycle. Furthermore, WYC02-9 induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9, caspase-3, and PARP. The above effects were all prevented by the ROS scavenger N-acetylcysteine. Administration of WYC02-9 in a nude mouse DU145 xenograft model further identified the anti-cancer activity of WYC02-9. These findings therefore suggest that WYC02-9-induced DNA damage and mitochondria-dependent cell apoptosis in DU145 cells are mediated via ROS generation.
No preview · Article · May 2011 · Free Radical Biology and Medicine
[Show abstract][Hide abstract]ABSTRACT: Eight new lupane triterpenes, including 7beta-cis-coumaroylbetulinic acid (1), 7beta-trans-coumaroylbetulinic acid (2), 7beta-cis-coumaroyl-3-epi-betulinic acid (3), 7beta-trans-coumaroyl-3-epi-betulinic acid (4), 7beta-cis-coumaroylbetulonic acid (5), 7beta-trans-coumaroylbetulonic acid (6), 7beta-hydroxybetulinaldehyde (7) and 28-norlup-20(29)-ene-3alpha,17beta-diol (8), together with fifteen known compounds were isolated from the bioactive methanol extract of the stems of Perrottetia arisanensis. The structures of the new compounds were elucidated by spectroscopic and HR-ESI-MS analysis. All new compounds were evaluated for their cytotoxicity against six human cancer cell lines. Among them, lupane triterpene coumaroyl esters 1-6 showed moderate cytotoxicity with IC (50) values ranging from 3.75 to 21.29 microM. This is the first report for lupane triterpenes with a phenylpropane moiety substituted at C-7.
[Show abstract][Hide abstract]ABSTRACT: Four new diterpenes, acasiane A ( 1), acasiane B ( 2), farnesirane A ( 3), and farnesirane B ( 4), along with three known diterpenes ( 5 - 7), two triterpenes ( 8 and 9), and eight flavonoids ( 10 - 17) were isolated from the roots of Acacia farnesiana. The structures and relative configurations of these compounds were determined by various spectroscopic and x-ray analyses. All isolated compounds were evaluated for their in vitro cytotoxic activities against six human cancer cell lines (Hep G2, Hep 3B, MDA-MB-231, MCF-7, A549, and Ca9 - 22) with the MTT method. Betulinic acid ( 8) displayed moderate cytotoxicity (1.70 - 5.74 microg/mL) towards five human cancer cell lines and the flavonoids had slight effects. In addition, 8, diosmetin ( 13), and 3',4',5-trihydroxy-7-methoxyflavone ( 15) slightly inhibited superoxide anion generation or elastase release by human neutrophils, indicating moderate anti-inflammatory activities.
[Show abstract][Hide abstract]ABSTRACT: Seven new lupane triterpenoids were isolated from bioactive methanol extracts of Microtropis fokienensis (1- 4) and Perrottetia arisanensis (4-7), along with 18 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data analysis. All triterpenoids were evaluated for their in vitro cytotoxicity toward seven human cancer cell lines. Compound 8 (28-hydroxy-3-oxo-lup-20(29)-en-30-al) was among the most cytotoxic substances obtained and was found to induce apoptosis of human leukemia HL60 cells and mediate cleavage of PARP and up-regulation of Bax proteins.
No preview · Article · Aug 2008 · Journal of Natural Products
[Show abstract][Hide abstract]ABSTRACT: Rehmanniae Radix (Di Huang) is one of the most important traditional Chinese medicines (TCM), and is used for multiple therapeutic purposes. In our investigation of the chemical constituents of Rehmanniae Radix, steamed roots were prepared by the classical processing method. Reversed-phase HPLC of the 50% MeOH extract of steamed Rehmanniae Radix yielded three 5-hydroxymethylfurfural derivatives. The new furfural disaccharide 5-(alpha-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranosyloxymethyl)-2-furancarboxaldehyde (1) was isolated and characterized, together with its known aglycone 5-hydroxymethyl-2-furfural (3), which is currently in sickle cell anemia Phase I clinical trials, and its corresponding monosaccharide 5-(alpha-D-glucopyranosyloxymethyl)-2-furancarboxaldehyde (2), which was isolated as a natural product for the first time. The presence of these three compounds, particularly 3, which were not found in the unprocessed extract of Rehmanniae Radix, could substantiate the traditional medicinal use of steamed Rehmanniae Radix.
No preview · Article · May 2008 · Journal of Natural Medicines
[Show abstract][Hide abstract]ABSTRACT: Angiogenesis is a critical step in tumor progression and involves several steps including endothelial cell (EC) proliferation, migration, and matrix remodeling. We investigated the antiangiogenic effects of 20( S)-protopanaxadiol ( 1) and 20( S)-protopanaxatriol ( 2), the sapogenins of two major ginseng saponins, in an angiogenesis model of human umbilical vein endothelial cells (HUVECs). These compounds inhibited the proliferative activity of HUVECs in a dose-dependent manner and have potential as anticancer drug candidates. In addition, we report the complete and unambiguous assignment of (1)H NMR spectra of 1 and 2, based on analyses of 2D NMR spectra including COSY, NOESY, HSQC, and HMBC. This report is the first to completely assign the (1)H NMR signals of 2, together with correction of data for 1 from prior reports.
[Show abstract][Hide abstract]ABSTRACT: Seven pure flavonolignans were isolated from an extract of milk thistle [Silybum marianum (L.) Gaertn (Astera-ceae)], by semipreparative reverse-phase HPLC, and identified based on spectroscopic and LC-MS=IT-TOF data. All seven compounds were screened as potential antitumor-promoting agents by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) acti-vation assay in Raji cells. They showed good inhibitory activity (87.7–94.9%) at 1000 mol ratio=TPA. Silychris-tin A (1) and silychristin B (2) were slightly more potent than the well-known antitumor promoter b-carotene. Silychristins A (1) and B (2) and isosilybins A (6) and B (7) were more active than the clinically proven cancer prevention components silybins A (4) and B (5).
Full-text · Article · Dec 2007 · Pharmaceutical Biology
[Show abstract][Hide abstract]ABSTRACT: In our continuing research on cytotoxic components from the Formosan pteridophyte Thelypteris torresiana (GAUD.) ALSTONONE, two new compounds, a novel flavonoid, flavotorresin (1), and a flavonoid diglycoside, multiflorin C (2), along with five known compounds, were isolated. The structural elucidation was established on the basis of spectroscopic data analysis. The possible biosynthetic pathway of the flavonoids from this fern is summarized.
Full-text · Article · Oct 2007 · CHEMICAL & PHARMACEUTICAL BULLETIN
[Show abstract][Hide abstract]ABSTRACT: Silychristins A (1) and B (2), silydianin (3), silybins A (4) and B (5), and isosilybins A (6) and B (7) are major bioactive flavonolignans in silymarin, a herbal remedy derived from the milk thistle Silybum marianum. In this study, the seven major active flavonolignans including the diastereomers 1/ 2, 4/ 5, and 6/ 7 were completely separated using semi-micro-high performance liquid chromatography (HPLC) with a Nucleosil 100-3 C 18 HD column and a MeOH/water/formic acid mobile phase system. The collision-induced dissociation (CID) MS/MS and MS (3) spectra of these flavonolignans were studied systematically using hybrid ion-trap and time-of-flight (IT-TOF) mass spectrometry. Efficient differentiation between the seven flavonolignans (1- 7) was possible based on comparison of the resultant CID-MS/MS or MS (3) spectra. Each characteristic MS/MS or MS (3) fragmentation pattern was elucidated with high-resolution mass spectra by IT-TOF. The results with the present methodology show that liquid chromatography-mass spectrometry IT-TOF (LC-MS/IT-TOF) can be useful for general screening of active natural products from plant extracts and for the specific quality control of silymarin.
No preview · Article · Oct 2007 · Journal of Natural Products
[Show abstract][Hide abstract]ABSTRACT: Protoapigenone (1), isolated from Thelypteris torresiana, previously showed significant cytotoxic activity against five human cancer cell lines. In a continued structure-activity relationship study, the first total synthesis and modification of 1 were achieved. All synthesized compounds and related intermediates were evaluated for cytotoxic activity against five human cancer cell lines, HepG2, Hep3B, MDA-MB-231, MCF-7, and A549. Among them, 24 showed 2.2-14.2-fold greater cytotoxicity than 1 and naphthyl A-ring analogues remarkably enhanced the activity.
[Show abstract][Hide abstract]ABSTRACT: Two new isomalabaricane-type triterpenes, stellettins L (1) and M (2), and three new sterols (3-5) were isolated from the marine sponge Stelletta tenuis collected in the South China Sea. Chemical structures were established from spectroscopic data and comparison with known compounds. In addition, spectroscopic data reported for the known sterol 24-methylene-27-methylcholest-5-en-3beta-ol-7-one (6) were revised. Compounds 1 and 2 exhibited significant cytotoxic activity against stomach cancer (AGS) in vitro.
Full-text · Article · Aug 2007 · Journal of Natural Products
[Show abstract][Hide abstract]ABSTRACT: During our search for anti-tumor agents from pteridophytes, three new flavonoids, protoapigenone (1), 5',6'-dihydro-6'-methoxyprotoapigenone (2), and protoapigenin (3), along with four known compounds, protoapigenin 4'- O-beta- D-glucoside (4), apigenin 4'- O-beta- D-glucoside (5), kaempferol 3- O-alpha- L-rhamnopyranoside (6), kaempferol 3,7-di- O-alpha- L-rhamnopyranoside (7), were isolated from Thelypteris torresiana using bioactivity-guided fractionation methods . The structures of the new isolates were elucidated by 1D- and 2D-NMR spectral analysis. Among the 7 compounds, protoapigenone (1) exhibited significant anti-tumor activities toward Hep G2, Hep 3B, MCF-7, A549, and MDA-MB-231 with IC50 values of 1.60, 0.23, 0.78, 3.88 and 0.27 microg/mL, respectively.
[Show abstract][Hide abstract]ABSTRACT: Bioactivity-directed fractionation led to the isolation of a new N-(methoxycarbonyl) phenanthrene alkaloid, romucosine I (1), along with three known N-(methoxycarbonyl) alkaloids, romucosine C (2), tuduranine (3), and promucosine (4). The structures of these compounds were identified on the basis of spectral data and chemical evidence. A proposed biogenesis about these isolates is also reported in this paper.