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Ya-Ching Shen

Publications and source records attributed to Ya-Ching Shen.

At least 19 recordsLinked to original sources
PubMed2006

Ilimaquinone, a marine sponge metabolite, displays anticancer activity via GADD153-mediated pathway.

The marine organisms produce many metabolic substances with numerous pharmacological activities. It has been suggested that ilimaquinone, a metabolite of sea sponge, can induce vesiculation of the Golgi apparatus and display several biological activities, such as anti-human immunodeficiency virus, anti-inflammation as well as anti-microbial activities. In this study, the sulforhodamine B assays showed that ilimaquinone induced a concentration-dependent anti-proliferative effect in several types of cancer cell lines, including prostate cancer PC-3 and LNCaP, non-small cell lung cancer A549 and hepatocellular carcinoma Hep3B cells. The anticancer mechanism of ilimaquinone in the representative PC-3 cells was identified. Ilimaquinone induced a time-dependent increase of G(1) phase arrest and a subsequent increase of hypodiploid sub-G(1) phase (apoptosis) of the cell cycle. The arrest of the cell cycle was associated with a sustained high level of nuclear cyclin E but the absence of DNA synthesis by flow cytometric analysis, indicating an incomplete S phase. Although ilimaquinone-induced Golgi vesiculation, the data showed that the inhibition of cancer cell growth was not through the Golgi fragmentation. Several biological kinases and transcription factors were examined in this study. The data demonstrated that ilimaquinone did not activate extracellular signal-regulated kinase and phosphatidylinositol 3-kinase but induce the up-regulation and nuclear translocation of growth arrest and DNA damage inducible gene 153 (CHOP/GADD153). Furthermore, ilimaquinone-mediated anti-proliferative effect is significantly reduced in the antisense CHOP/GADD153-overexpressing cells. Ilimaquinone also inhibited DNA binding of NF-kappaB; however, this inhibitory effect could not explain ilimaquinone-induced anticancer effect. In summary, it is suggested that ilimaquinone induces the anti-proliferative effect through the G(1) arrest of the cell cycle and the up-regulation and nuclear translocation of CHOP/GADD153.

Active Transport, Cell Nucleus↗
PubMed2006

Induction of Fas clustering and apoptosis by coral prostanoid in human hormone-resistant prostate cancer cells.

Cyclopentenone prostaglandins (PGs) such as PGA1, PGA2 and delta12-PGJ2 have been shown to suppress tumor cell growth and to induce apoptosis in prostate cancer cells. Bromovulone III, which is isolated from the soft coral Clavularia viridis, is a cyclopentenone prostanoid. In this study, the anti-tumor activity as well as action mechanism of bromovulone III was identified in prostate cancer cells. Bromovulone III displayed anti-tumor activity of 30 to 100 times more effective than PGA1, PGA2 and delta12-PGJ2 in PC-3 cells. Several targets of caspases and Bcl-2 family of proteins were detected and the data demonstrated that bromovulone III induced the activation of caspase-8, -9 and -3, and Bid cleavage in which the caspase-8 activation occurred the first. Bromovulone III did not modify the protein levels of death receptors and ligands. Of note, the Fas clustering in PC-3 cells responsive to bromovulone III was observed by confocal immunofluorescence microscopy suggesting the involvement of Fas-mediated pathway. Bromovulone III also induced the cleavage of Mcl-1 in this study. The cleavage fragments (24, 19 and 17 kDa) may partly share the apoptotic insult. Although it has been suggested that Fas-mediated signaling may contribute to the caspase-8 activation induced by DNA-damaging agents; however, bromovulone III did not induce any DNA breakage, suggesting that bromovulone III-induced Fas/caspase-8-dependent signaling is not through the direct target on DNA damage. In summary, the data suggest that bromovulone III causes a rapid redistribution and clustering of Fas in PC-3 cells. Subsequently, the Fas event causes the activation and interaction of caspase-8/Bid/caspase-9 signaling cascades, and the activation of executor caspase-3.

Animals↗
PubMed2006

Isolation of aureol from Smenospongia sp. and cytotoxic activity of some aureol derivatives.

The sesquiterpene aureol (1) was isolated by chromatographic fractionation of a non-polar extract from Smenospongia sp. Methylation of aureol yielded 5'-O-methyl-aureol (2) while the prepared acylation products of aureol were 5'-O-acetyl-aureol (3), 5'-O-benzoyl-aureol (4), 5'-O-(4-fluoro-benzoyl)-aureol (5), 5'-O-(4-chlorobenzoyl)-aureol (6), 5'-O-(4-methylbenzoyl)-aureol (7), 5'-O-nicotinoyl-aureol (8), aureol-N,N-dimethylthiocarbamate (9), 5'-O-(2-furoylcarbonyl)-aureol (10), 5'-O-(2-thienoylcarbonyl-aureol (11). The structures of aureol as well as its ten derivatives were established through spectral analysis. The in vitro cytotoxic activities of the eleven compounds were evaluated against Hepa59T/VGH, KB and Hela tumor cell lines.

Animals↗
PubMed2006

Cespitulactones A and B, new diterpenoids from Cespitularia taeniata.

Two new diterpenoids, designated cespitulactones A (1) and B (2), were isolated from a sample of the soft coral Cespitularia taeniata collected in Taiwan. Compound 1 possesses a novel structure with a bond cleavage between C-10 and C-11, and having a 14-membered lactone ring junction between C-10 and C-12. Their structures were elucidated on the basis of extensive spectroscopic analysis and chemical derivatization. The isolated compounds were also evaluated for cytotoxicity toward human cancer cell lines.

Animals↗
PubMed2006

Xenicane-type diterpenes with cytotoxicity from Xenia florida.

Chromatographic investigation of an acetone extract of the octocoral Xenia florida afforded three new xenicane diterpenes, namely, florxenilide A (1), florxenilide B (2), and florxenilide C (3), in addition to seven known xenicane diterpenes and two known cadinene sesquiterpenes. Structures were elucidated through spectroscopic analysis, especially 2D NMR, and chemical derivatization. The absolute configuration of 1 was determined by NOESY, CD, and Mosher's methods. Florxenilides A (1) and B (2) exhibited cytotoxicity against human colon cancer (WiDr) cells at 4.5 and 3.7 muM, respectively.

Animals↗
PubMed2006

C18 dibenzocyclooctadiene lignans from Kadsura philippinensis.

Four new C18 dibenzocyclooctadiene lignans, kadsuphilins A (1) and B (3), 6-epi-gomisin (2), and 1-demethylkadsuphilin A (4), along with eight known related metabolites, were isolated from an EtOAc fraction of an alcoholic extract of the aerial parts of Kadsura philippinensis growing in Taiwan. The structures of 1-4 were elucidated on the basis of spectroscopic analyses, including 2D NMR (HMQC, HMBC, and NOESY) experiments, and by comparison of their spectroscopic data with those of related metabolites. The configurations of the biphenyl and cyclooctadiene moieties were deduced from circular dichroism (CD) and NOESY NMR spectra, respectively. Some of the compounds showed radical-scavenging activity in a DPPH-HPLC method.

Biphenyl Compounds↗
PubMed2005

Taiwankadsurins A, B, and C, three new C19 homolignans from Kadsura philippinensis.

[structures: see text] Three novel C19 homolignans, designated taiwankadsurins A (1), B (2), and C (3), were isolated from the aerial parts of Taiwanese medicinal plant Kadsura philippinensis. The structures of 1-3, which have a 3,4-{1'-[(Z)-2''-methoxy-2''-oxo-ethylidene]}-pentano(2,3-dihydro-benzo[b]furano)-3-(2'''-methoxycarbonyl-2'''-hydroxy-2''',3'-epoxide) skeleton, were determined by spectroscopic analyses, especially 2D NMR techniques (HMBC and NOESY). Compound 2 exhibited mild cytotoxicity against human KB and Hela tumor cells.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Kadsuphilactones A and B, two new triterpene dilactones from kadsuraphilippinensis.

[structure: see text]. Two novel triterpene dilactones, kadsuphilactones A (1) and B (2), were isolated from the Taiwanese medicinal plant Kadsura philippinensis. The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic methods, including two-dimensional NMR techniques, and confirmed by X-ray crystallographic analysis. Kadsuphilactone B (2) exhibited in vitro anti-HBV activity with IC(50) values of 6 microg/mL by HBsAg enzyme immunoassay.

Antiviral Agents↗
PubMed2005

Syntheses of C(18) dibenzocyclooctadiene lignan derivatives as anti-HBsAg and anti-HBeAg agents.

(+)-Gomisin K(3) (1) and kadsurarin (2) were isolated from Schizandra arisanensis and Kadsura matsudai, respectively, and a series of C(18) dibenzocyclooctadiene lignan analogues (5-20) derived from 1 and 2 were synthesized. Esterified derivatives of 1 and 2 were evaluated for inhibitory activity against human type B hepatitis with surface antigen (HBsAg) and e antigen (HBeAg). Most of the analogues (5-8, 10, 12-13) derived from 1 exhibited higher anti-HBsAg effects and lower toxicity, and 6, 7, 8 and 12 also showed higher anti-HBeAg activity. Among these active C(18) dibenzocyclooctadiene lignan analogues, the lignan with a but-3-enoyl group (6) exhibited the most active inhibition.

Antiviral Agents↗
PubMed2005

New gemacranolides from Eupatorium hualienense.

Phytochemical investigation of Eupatorium hualienense (C. H. Ou, S. W. Chung, C. I. Peng) has resulted in the isolation of the new sesquiterpene lactones 1-5, named eupahualins A-E, along with the known heliangolide eupasimplicin B (6). The structures of the isolated compounds were established through detailed spectral analyses, especially by means of 2D-NMR techniques. Compounds 1-4 and 6 showed significant activities against cell lines of human chronic myelogenous leukemia (K562) and human bone cancer (U2OS).

Antineoplastic Agents↗
PubMed2005

Investigation of anticancer mechanism of clavulone II, a coral cyclopentenone prostaglandin analog, in human acute promyelocytic leukemia.

The marine prostanoid clavulones were shown to exert cytotoxicity against several cancer cells. In the present study, we illustrate the pathways utilized by clavulone II to trigger apoptotic signaling in human acute promyelocytic leukemia HL-60 cells. Exposure of cells to clavulone II resulted in early induction of phosphatidylserine externalization, mitochondrial dysfunction, and alteration of the cell cycle. Down-regulated expression of cyclin D1 explained the effect of clavulone II on G1 phase arrest of the cell cycle. Clavulone II induced the disruption of mitochondrial membrane potential and activation of caspase-8, -9 and -3 in a time- and concentration-dependent manner. Furthermore, the effect of 3 microM clavulone II was accompanied by the up-regulation of Bax, down-regulation of Mcl-1, and cleavage of Bid. Taken together, it is suggested that low concentrations of clavulone II induce the antiproliferative effect through the down-regulation of cyclin D1 expression and G1 arrest of the cell cycle, while that of high concentration induce the apoptotic cell death via the modulation of members of caspases and Bcl-2 family proteins in HL-60 cells.

Animals↗
PubMed2005

The beta-carboline analog Mana-Hox causes mitotic aberration by interacting with DNA.

Mana-Hox, an analog of beta-carbolines with anticancer activity, induces aberrant mitosis and delays mitotic exit. However, the cellular target is not known. In this study, we visualized the intracellular localization of Mana-Hox. Mana-Hox rapidly penetrated into cells (within 1 min) and concentrated on disorganized metaphase chromosomes after 13 hr of exposure. We demonstrated that Mana-Hox is a noncovalent DNA binder that can interact with DNA through intercalation and/or through minor groove binding. Furthermore, Mana-Hox also inhibits topoisomerase II relaxation activity in vitro, suggesting that Mana-Hox could perturb mitotic chromosome decatenation. Overall, Mana-Hox binding to DNA plays a critical role in the induction of aberrant mitosis and contributes to its anticancer activity.

Antineoplastic Agents↗
PubMed2005

Induction of endoplasmic reticulum stress and apoptosis by a marine prostanoid in human hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma is a very common malignancy and is highly chemoresistant to currently available chemotherapeutic agents. We isolated a marine prostanoid, bromovulone III, from soft coral Clavularia viridis and found that it displayed effective anti-tumor activity in human hepatocellular carcinoma. The anti-tumor mechanism has been delineated in this study. METHODS: Anti-tumor efficacy and apoptotic cell death were examined by sulforhodamine B and Hoechst 33342 assays. Rhodamine 123 was used to measure the change of mitochondrial membrane potential. Immunoprecipitation and Western blotting detect the involvement of several apoptosis-related proteins. Electron microscopic examination detects the morphological change of mitochondria and endoplasmic reticulum (ER). RESULTS: Bromovulone III primarily induced mitochondria-related activation of caspase-9 and -3 in several tumor types, such as prostate cancer PC-3 and acute promyelocytic leukemia HL-60 cells. However, it primarily induced the activation of m-calpain, caspase-12, and transcription factor CHOP/GADD153 in hepatocellular carcinoma Hep3B cells, suggesting the involvement of ER stress. Furthermore, a secondary mitochondrial swelling and depolarization of mitochondrial membrane potential were subsequently triggered after ER stress, suggesting the crosstalk between ER and mitochondria. CONCLUSIONS: It is suggested that bromovulone III induces apoptosis in Hep3B cells through a mechanism that induces ER stress and leads to activation of CHOP/GADD153 and caspase-12.

Apoptosis↗
PubMed2005

Three new taxane diterpenoids from Taxus sumatrana.

Phytochemical investigation of taxane diterpenoidal content of an acetone extract of the leaves and twigs of Taxus sumatrana has resulted in the isolation of three new taxoid compounds, tasumatrols E (1), F (2), and G (3) together with 13 known taxanes (5-16). The structures of these taxanes as well as their derivatives were established on the basis of spectroscopic analyses, especially 1D and 2D NMR. Compounds 1, 2, 12, and 16 exhibited significant cytotoxicity against human A-498, NCI-H226, A549, and PC-3 tumor cells.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Cytotoxic sesquiterpene lactones from Eupatorium kiirunense, a coastal plant of Taiwan.

Phytochemical investigation of Eupatorium kiirunense has resulted in the isolation of eight new sesquiterpene lactones, constituted by five germacranolides, eupakirunsins A-E (1-5), and three heliangolides, eupaheliangolide A (6), 15-acetoxyheliangin (7), and 3-epi-heliangin (8), in addition to the known heliangin (9) and 8,10-epoxy-9-acetoxythymol angelate (10). The structures of the new compounds were established through detailed analysis of their spectroscopic data. Compounds 6, 8, and 9 exhibited cytotoxicity against human oral epidermoid (KB), cervical epitheloid (Hela), and liver (hepa59T/VGH) carcinoma cells.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Cytotoxic clerodane diterpenoids from Casearia membranacea.

Bioassay-guided fractionation of the EtOAc extract of Casearia membranacea leaves and twigs afforded three new clerodane diterpenes, caseamembrins M-O (1-3), and the known rel-(2S,5R,6R,8S,9S,10R,18S,19R)-2-(2-methylbutyryloxy)-6-hydroxy-18,19-di-O-acetyl-18,19-epoxycleroda-3,13(16),14-triene (4) and caseamembrin D (5). The structures of 1-3, including the relative configurations, were established by extensive NMR spectroscopic analyses. The cytotoxic activities of the isolated diterpenoids against human oral epidermoid (KB), medulla (Med), and colon (DLD-1) cancer cell lines were evaluated.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Antihepatitis activity (anti-HBsAg and anti-HBeAg) of C19 homolignans and six novel C18 dibenzocyclooctadiene lignans from Kadsura japonica.

Bioassay-directed fractionation of the EtOAc extract of Kadsura japonica has led to the isolation of six new C18 dibenzocyclooctadiene lignans, schizanrins I, J, K, L, M, N, along with four known C19 homolignans, taiwanschirins A, B, C, and heteroclitin F. The elucidations of the new structures were based on spectral analysis. Bioassay evaluation against human type B hepatitis revealed that taiwanschirins A and B showed strong activity for anti-HBsAg and a medium effect for anti-HBeAg at 25 microg/mL (12.9 and 11.9 microM for taiwanschirins A and B, respectively).

Antiviral Agents↗