Antitumor effect of resorcinol derivatives from the roots of Ardisia brevicaulis by inducing apoptosis

Two new resorcinol derivatives 2-methoxy-4-hydroxy-6-(8Z-pentadecenyl)-benzene-1-O-acetate (1) and 2-methoxy-4-hydroxy-6-pentadecyl-benzene-1-O-acetate (2), together with four known compounds 2-methoxy-4-hydroxy-6-tridecyl-benzene-1-O-acetate (ardisiphenol D, 3), 5-(8Z-pentadecenyl)resorcinol (4), 5-pentadecylresorcinol (5), 5-tridecylresorcinol (6), have been isolated from the roots of Ardisia brevicaulis in our previous work. In the present study, the inhibitory effect of 1–6 on the proliferation of human pancreatic PANC-1, human lung A549, human gastrointestinal carcinoma SGC 7901, human breast MCF-7, and human prostate PC-3 cancer cells was evaluated by the methyl thiazolyl tetrazolium method. Compounds 1–6 all showed inhibitory activities against the proliferation of PANC-1, A549, SGC7901, MCF-7, and PC-3 cancer cells. Compound 3, the most active agent and the main constituent with the highest yield, induced apoptosis of PANC-1 cells (the most sensitive cell line among the cell lines screened) via the activation of caspase-3 and caspase-9, up-regulation of the ratio of bax/bcl-2 protein expression.     

Ardisiphenol D,a resorcinol derivative identified from Ardisia brevicaulis,exerts antitumor effect through inducing apoptosis in human non-small-cell lung cancer A549 cells

Context: The in vitro and in vivo antitumor activities of ardisiphenol D, a natural product isolated from the roots of Ardisa brevicaulis Diels (Myrsinaceae), have been studied.

Objective: Previously, we have isolated and identified some chemical constituents from this plant. Furthermore, these compounds showed significant inhibition of the proliferation of human pancreatic PANC-1, human lung A549, human gastrointestinal carcinoma SGC 7901, human breast MCF-7, and human prostate PC-3 cancer cells. In the present paper, a major resorcinol derivative called ardisiphenol D was further studied for its antitumor mechanism.

Materials and methods: MTT assay was used to detect the proliferation of A549 cancer cells. Apoptosis induced by ardisiphenol D was observed by Hoechst 33258 fluorescence staining. Caspase-3 enzyme activity was measured by a commercial caspase-3 enzyme activity detection kit. Protein expression of bax, bcl-2, and caspase-3 was tested by Western blots. In vivo antitumor activity of ardisiphenol D was evaluated by determination of A549 tumor growth in nude mice.

Results: Ardisiphenol D significantly inhibited the proliferation of A549 cells with an IC₅₀ of 0.997?μM with a 48?h treatment. Hoechst 33258 fluorescence staining results indicated the apoptosis of A549 cells induced by 3.125?μM of ardisiphenol D. About 0.39 and 0.78?μM of ardisiphenol D also potently increased the caspase-3 enzyme activity in 24?h. Furthermore, 0.39–3.125?μM of ardisiphenol D induced the activation of caspase-3 protein and the up-regulation of the ratio of bax/bcl-2 protein expression in A549 cells. After i.p. injection, ardisiphenol D (5?mg/kg) also strongly suppressed the A549 tumor growth in nude mice.

Discussion and conclusion: Ardisiphenol D induced apoptosis of A549 cells via activation of caspase-3 and up-regulation of the ratio of bax/bcl-2 protein expression. Ardisiphenol D also strongly suppressed the A549 tumor growth in nude mice and exerted antitumor activity in vivo.     

Four new benzofurans from seeds of Styrax perkinsiae

Four new benzofurans trans-5-(3-hydroxypropyl)-7-methoxy-2-[2,3-dihydro-3-hydroxymethyl-7-methoxy-2-(3-methoxy-4-hydroxyphenyl)-benzofuran-5-yl]benzofuran (1), (E)-5-(2-formylvinyl)-7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran (2), 5-(3-butanoyloxypropyl)-7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran (3), and 5-(3-hydroxypropyl)-7-hydroxy-2-(3,4-methylenedioxyphenyl) benzofuran (4) were isolated from the seeds of Styrax perkinsiae, together with egonol (5), demethoxyegonol (6), egonol acetate (7), demethoxyegonol acetate (8), egonol glucoside (9), egonol gentiobioside (10), egonol gentiotrioside (11), beta-sitosterol (12), and beta-daucosterol (13). Their structures were established by spectroscopic and chemical methods. Compounds 1 and 4 exhibited cytotoxic activity in vitro using two breast cancer cell lines MCF-7 and MDA-MB-231.     

Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR

AIM: To investigate the reversal effects of curcumin on multidrug resistance (MDR) in a resistant human gastric carcinoma cell line. METHODS: The cytotoxic effect of vincristine (VCR) was evaluated by MTT assay. The cell apoptosis induced by VCR was determined by propidium iodide (PI)-stained flow cytometry (FCM) and a morphological assay using acridine orange (AO)/ethidium bromide (EB) dual staining. P-glycoprotein (P-gp) function was demonstrated by the accumulation and efflux of rhodamine123 (Rh123) using FCM. The expression of P-gp and the activation of caspase-3 were measured by FCM using fluorescein isothiocyanate (FITC)-conjugated anti-P-gp and anti-cleaved caspase-3 antibodies, respectively. RESULTS: Curcumin, at concentrations of 5 micromol/L, 10 micromol/L, or 20 micromol/L, had no cytotoxic effect on a parent human gastric carcinoma cell line (SGC7901) or its VCR-resistant variant cell line (SGC7901/VCR). The VCR-IC50 value of the SGC7901/VCR cells was 45 times more than that of the SGC7901cells and the SGC7901/VCR cells showed apoptotic resistance to VCR. SGC7901/VCR cells treated with 5 micromol/L, 10 micromol/L, or 20 micromol/L curcumin decreased the IC50 value of VCR and promoted VCR-mediated apoptosis in a dose-dependent manner. Curcumin (10 micromol/L) increased Rh123 accumulation and inhibited the efflux of Rh123 in SGC7901/VCR cells, but did not change the accumulation and efflux of Rh123 in SGC7901 cells. P-gp was overexpressed in SGC7901/VCR cells, whereas it was downregulated after a 24-h treatment with curcumin (10 micromol/L). Resistant cells treated with 1 mumol/L VCR alone showed 77% lower levels of caspase-3 activation relative to SGC7901 cells, but the activation of caspase-3 in the resistant cell line increased by 44% when cells were treated with VCR in combination with curcumin. CONCLUSION: Curcumin can reverse the MDR of the human gastric carcinoma SGC7901/VCR cell line. This might be associated with decreased P-gp function and expression, and the promotion of caspase-3 activation in MDR cells.     

Synthesis and structural characterization of derivatives of 2- and 3-benzo[b]furan carboxylic acids with potential cytotoxic activity

Derivatives of 2- and 3-benzo[b]furancarboxylic acids were prepared and evaluated for their cytotoxic potential in the National Cancer Institute, Bethesda, USA. Six compounds: 7-acetyl-6-hydroxy-3-methyl-2-benzofurancarboxylic acid (2), 6-hydroxy-7-(p-methoxycinnamoyl)-3-methyl-2-benzofurancarboxylic acid (4), 5-bromo-7-hydroxy-6-methoxy-2-benzofurancarboxylic acid methyl ester (6a), 6-acetyl-5-(O-ethyl-2'-diethylamino)-2-methyl-3-benzofurancarboxylic acid methyl ester (1f), 6-(O-ethyl-2'-diethylamino)-7-p-methoxycinnamoyl)-3-methyl-2-benzofurancarboxylic acid methyl ester hydrochloride (4b), 5-bromo-7-(O-ethyl-2'-diethylamino)-6-methoxy-2-benzofurancarboxylic acid methyl ester (6b) showed significant cytotoxic activities against human cancer cell lines. In addition the crystal structures of 7-methoxy-2-benzofurancarboxylic acid methyl ester (7a) has been solved by X-ray structure analysis of single crystals.     

Sesquiterpene lactones with potent cytotoxic activities from Vernonia chinensis

Five new sesquiterpene lactones, namely vernchinilides A-E (1-5), along with five known compounds, 8 beta-(2-methylacryloyloxy)hirsutinolide 13-O-acetate (6), 8 alpha-(2-methylacryloyloxy)-1beta,4beta-epoxy-1alpha-methoxy-13-O-acetate-10 betaH-germacra-5 E,7(11)-dien-12,6-olide (7), 8 beta-(2-hydroxymethylacryloyloxy)hirsutinolide 13-O-acetate (8), 8 alpha-tigloyloxyhirsutinolide 13-O-acetate ( 9) and vernolide-B (10) were isolated from Vernonia chinensis. The structures of these new compounds were elucidated on the basis of spectral data, especially 2D-NMR techniques. Compounds 2, 5 and 6 exhibited potent cytotoxic activities against P-388 and A-549 tumor cell lines.     

Constituents of Knema laurina and Knema tenuinervia ssp. setosa

Extraction of the stem bark of KNEMA LAURINA Warb. and KNEMA TENUINERVIA W. J. J. O. de Wilde ssp. SETOSA de Wilde furnished 3-(12-phenyl-8 Z-dodecenyl)-phenol and 3-(8 Z-pentadecenyl)-phenol together with 8-hydroxy-6-methoxy-3- N-pentylisocoumarin, respectively. 2-Carboxy-3-(12-phenyldodecyl)-phenol) and 2,4-dihydroxy-6-(10-phenyldecyl)-acetophenone were common to both extracts.     

Pyrenes and pyrendiones from Uvaria lucida

A chemical investigation of the chloroform extract of the roots of Uvaria ludida Benth. (Annonaceae), an important African traditional medicine, led to the isolation of six new compounds; three pyrenes, 2-hydroxy-1,8-dimethoxypyrene (1), 8-methoxy-1,2-methylenedioxypyrene (2), and 7-hydroxy-8-methoxy-1,2-methylenedioxypyrene (3), two pyrenediones, 2-hydroxy-1,8-pyrenedione (4) and 2-methoxy-1,8-pyrenedione (5), and a sesquiterpene, (-)-10-oxo-isodauc-3-en-15-oic acid (6), together with eight known compounds (7-14). The structural elucidation by spectroscopic studies of the compounds isolated is described. While pyrenes did not exhibit strong cytotoxicity against human promyelocytic leukemia HL-60 cells, pyrenediones showed strong cytotoxicity. The IC(50) of 4 was 70 ng mL(-1), which was close to that of etoposide (IC(50) = 60 ng mL(-1)).     

New prenylated metabolites of Deguelia longeracemosa and evaluation of their antimicrobial potential

The analysis of root extracts from Deguelia longeracemosa (Benth.) A.M.G. Azevedo yielded fifteen prenylated metabolites. Nine of them are novel, and their molecular structures were determined through spectral analyses (UV, IR, MS and NMR) as being five derivatives of 4-hydroxy-3-phenylcoumarin: 4-hydroxy-3-(4'-hydroxyphenyl)-5-methoxy-6-(8',9'-epoxy-9'-methylbutyl)-2',2'-dimethylpyrano-(5',6':8,7)-coumarin; 4-hydroxy-3-(3',4'-methylenedioxyphenyl)-5-methoxy-6-(3,3-dimethylallyl)-2',2'-dimethypyrano-(5',6':8,7)-coumarin; 4-hydroxy-3-(3'-hydroxy-4'-methoxyphenyl)-5-methoxy-6-(3,3-dimethylallyl)-2',2'-dimethylpyrano-(5',6':8,7)-coumarin; 4-hydroxy-3-(3'-hydroxy-4'-methoxyphenyl)-5-methoxy-2',2'-dimethylpyrano-(5',6':6,7)-coumarin and 4-hydroxy-3-[4'-O-(3,3-dimethylallyl)phenyl]-5-methoxy-2',2'-dimethylpyrano-(5',6':6,7)-coumarin, three derivatives of 1,2-diphenyl-1,2-ethanodione (alpha-oxodeoxybenzoin derivatives): 1-[6-hydroxy-2-methoxy-3-(3,3-dimethylallyl)-2',2'-dimethylpyrano-(5',6':5,4)- ]-2-(4'-hydroxyphenyl)-1,2-ethanedione; 1-[6-hydroxy-2-methoxy-2',2'-dimethylpyrano-(5',6':3,4)]-2-(4'-methoxyphenyl)-1,2-ethanedione; 1-[6-hydroxy-2-methoxy-2',2'-dimethylpyrano-(5',6':3,4)]-2-(3',4'-methylenedioxyphenyl)-1,2-ethanedione and one derivative of deoxybenzoin: 2,4'-dimethoxy-6-hydroxy-2',2'-dimethylpyrano-(5',6':3,4)-deoxybenzoin. The antimicrobial activity of roots extracts and some isolated compounds was screened through bioautography against bacteria and fungi.     

Cytotoxic effects of sesquiterpene lactones from the flowers of<Emphasis Type="Italic">Hemisteptia lyrata</Emphasis> B

Four guaia-12,6-olide type sesquiterpene lactones, aguerin B (1), 8alpha-acetoxyzaluzanin C (2), cynaropicrin (3), and deacylcynaropicrin (4), were isolated from the flowers of Hemisteptia lyrata Bunge. It is the first report on the isolation of compounds 1-4 from Hemisteptia species. All the isolates (1-4) were examined for their cytotoxic activity against SK-OV-3, LOX-IMVI, A549, MCF-7, PC-3, and HCT-15 human cancer cell lines.     

用GC-MS法分析姜黄和片姜黄中挥发油成分并研究其体外抗肿瘤作用简

目的：分析姜黄和片姜黄中的挥发油成分,对其体外抗肿瘤作用进行研究.方法：采用水蒸气蒸馏法提取两种药材饮片中的挥发油,用GC MS法对挥发油成分做鉴别和分析.采用四甲基偶氮唑盐（MTT）法,以A-549人肺癌细胞株和SGC-7901人胃癌细胞株研究姜黄和片姜黄中挥发油成分的体外抗肿瘤作用.结果：姜黄和片姜黄中挥发油成分的含量分别为1.5％和1.2％.姜黄挥发油的主要成分为β-姜黄酮、芳姜黄烯、β-倍半水芹烯、吉玛酮和姜烯等,抑制A-549人肺癌细胞株和SGC-7901人胃癌细胞株的IC50分别为227.8和129.7 μg/ml.片姜黄挥发油的主要成分为莪术二酮、1,8-桉树脑、吉玛酮、异莪术醇、莪术醇和樟脑等,抑制A-549人肺癌细胞株和SGC-7901人胃癌细胞株的IC50分别为202.1和230.0 μg/ml.结论：姜黄和片姜黄中的挥发油成分有显著差异,两种挥发油对A-549人肺癌细胞株和SGC-7901人胃癌细胞株均有较弱的抑制作用.     

New cassaine diterpenoid amides with cytotoxic activities from the bark of Erythrophleum fordii

A phytochemical investigation of the bark of Erythrophleum fordii led to six new cassaine diterpenoid amides (2, 4-8), together with two known compounds of the same skeleton, nor-cassamide ( 1) and nor-erythrosuamide (3). The structures were mainly established on the basis of 1D, 2D NMR and HR-MS analysis. The compounds 1, 2, 4, 6-8 exhibited selective cytotoxic activities (IC50 values < 10 microM) against A2780, KB, Bel-7402, BGC-823, MCF-7, HCT-8, Hela, PC-3M, A549 and Ketr3 human cancer cell lines in the MTT test.     

Two new derivatives of griseofulvin from the mangrove endophytic fungus Nigrospora sp. (strain No. 1403) from Kandelia candel (L.) Druce

Two new compounds, methyl 3-chloro-6-hydroxy-2-(4-hydroxy-2-methoxy-6-methylphenoxy)-4-methoxybenzoate (1) and (2 S,5' R,E)-7-hydroxy-4,6-dimethoxy-2-(1-methoxy-3-oxo-5-methylhex-1-enyl)-benzofuran-3(2H)-one (2), together with four known compounds, griseofulvin (3), dechlorogriseofulvin (4), bostrycin (5), and deoxybostrycin (6), were isolated from the marine endophytic fungus NIGROSPORA sp. (No.?1403) collected from the South China Sea. The structures were elucidated by spectroscopic methods, 1D, 2D NMR, and HREIMS. Compounds 5 and 6 showed moderate antitumor and moderate antimicrobial activity.     

Dihydrotanshinone induces apoptosis of SGC7901 and MGC803 cells via activation of JNK and p38 signalling pathways

Context: Dihydrotanshinone (DHT), a natural compound from Salvia miltiorrhiza Bunge (Lamiaceae), showed higher cytotoxic potential compared with other tanshinones. Its effect and mechanism on gastric cancer have not been investigated.

Objective: This study evaluates the effects of DHT on cell proliferation and apoptosis on gastric cancer cells, and elucidates its molecular mechanisms.

Materials and methods: Human gastric cancer MGC803 and SGC7901 cells were treated with various concentrations of DHT (0–15?μM) for 24 and 48?h, and cell growth was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cell apoptosis was analysed by flow cytometry and DAPI staining. Western blots were performed to investigate changes in the level of apoptosis related genes in gastric cancer cell.

Results: DHT exhibited obvious inhibition of the survival of gastric cancer cells. The IC₅₀ values in SGC7901 and MGC803 cells were 9.14 and 5.39?μM for 24?h, respectively. Cells treated with 6?μM DHT resulted in 41.3% and 35.4% apoptotic cell fractions in SGC7901 and MGC803 cells, respectively, significantly higher than that of the control. Hallmarks of apoptosis were observed in gastric cancer cells after DHT exposure. DHT enhanced the expression levels of cleaved caspase-3, caspase-9 and poly-ADP-ribose polymerases. Furthermore, DHT increased the phosphorylation of JNK and p38 in SGC7901 and MGC803 cells.

Conclusion: DHT induced growth inhibition and apoptosis of gastric cancer cells, involving activation of caspase proteins and the JNK/p38 signaling pathway. The results indicated that DHT has a promising chemotherapeutic potential for human gastric cancer.     

Cytotoxic terpenoid and immunosuppressive phenolic glycosides from the root bark of Dictamnus dasycarpus

Five new compounds, two degraded terpene glycosides, dasycarpusides A and B (1, 2), and three phenolic glycosides, 2-methoxy-4-hydroxymethylphenol 1-O-alpha-rhamnopyranosyl-(1"-->6')- beta-glucopyranoside ( 3), 2-methoxy-4-acetylphenol 1-O-alpha-rhamnopyranosyl-(1"-->6')-beta-glucopyranoside (4), and 2-methoxy-4-(8-hydroxyethyl)-phenol 1-O-alpha-rhamnopyranosyl-(1"-->6')-beta-glucopyranoside (5), were isolated from the water-soluble constituents of the root bark of Dictamnus dasycarpus Turcz.(Rutaceae). Their structures were elucidated by spectroscopic analysis and chemical evidence. Moreover, it was found that dasycarpuside A (1) showed weak cytotoxic activity against A-549 (human lung adenocarcinoma) cell line, while 4 and 5 showed more remarkable activity of inhibiting the proliferation of T-cells in vitro.     

Three new sesquiterpenes from the stems of Nicotiana tabacum and their bioactivities

Three new sesquiterpenes, methyl 4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (1), methyl 2-hydroxy-4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (2), and methyl 2-hydroxy-6-(hydroxymethyl)-4-isopropyl-7-methoxynaphthalene-1-carboxylate (3), together with three known sesquiterpenes (4–6), were isolated from the stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. The results showed that compounds 2, 3, and 5 exhibited high anti-TMV activity with inhibition rates of 33.6, 35.8, and 36.7%. Compounds 1–6 showed weak inhibitory activities against some tested human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC₅₀ values in the range of 6.7–9.6 μM.     

6,8-二-三氟甲基-5-羟基-7-乙酰基白杨素的抗肿瘤作用

目的　研究 6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素的抗肿瘤作用及机制。方法　采用MTT比色法检测白杨素及白杨素乙酰化、卤化、三氟甲基化衍生物体外抗肿瘤活性 ;小鼠Lewis肺癌移植瘤模型观察目标化合物 (6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素 )体内抗肿瘤作用 ;PI染色流式细胞术分析 6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素对人胃癌(SGC 790 1 )细胞周期的影响。结果　白杨素及白杨素乙酰化、卤化、三氟甲基化衍生物对体外培养人胃癌 (SGC 790 1 )细胞 ,人急性粒细胞性白血病 (HL 6 0 )细胞和人结肠癌 (HT 2 9)细胞具有抑制增殖作用 ;以 6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素作用最强 ,其对SGC 790 1细胞 ,HT 2 9细胞和HL 6 0细胞的IC50 分别是 2 5 1 ,1 96和 0 1 8μmol·L-1 。 6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素对小鼠Lewis肺癌皮下移植原发瘤及自发性肺转移具有抑制作用 ,呈剂量依赖关系。6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素 (1～ 2 μmol·L-1 )能使SGC 790 1细胞周期阻滞于G1 期。结论　 6 ,8 二 三氟甲基 5 羟基 7 乙酰白杨具有抗肿瘤作用 ,其机制可能与使细胞周期G1 期阻滞相关     

中国南海石珊瑚Stylophora pistilata化学成分研究

目的 研究中国南海石珊瑚Stylopgora Stylophora pistillata的化学成分。方法 运用硅胶、凝胶(Sephadex LH-20)等多种柱色谱手段对化合物进行分离纯化；利用核磁共振、质谱等波谱学手段并结合其理化性质及文献数据鉴定化合物的结构。结果 从石珊瑚Stylopgora Stylophora pistillata的乙醇提取物中共分离鉴定了8个单体化合物：1,3-十四烷酸甘油二酯（1），正二十五烷（2），正二十三烷（3），肉豆蔻酸（4），2, 2"-氧代双(1, 4-二叔丁苯)（5），(R)-2-乙基己醇（6），2, 2"-bis(4-hydroxyphenyl)propane bis(2,3-epoxypropyl)ether（7）和5-hydroxy-3,4-dimethy-5- pentyl-2(5H)-furanone（8）。结论 化合物1～8均为首次从该石珊瑚中分离得到。细胞毒活性测试结果表明，化合物7对人慢性髓原白血病细胞（K562）、人肝癌细胞（BEL-7402）、人胃癌细胞（SGC-7901）、人肺癌细胞（A549）和人宫颈癌细胞(Hela)的增殖显示出一定的生长抑制活性，其余化合物对上述肿瘤细胞均无生长抑制活性。     

三氧化二砷(As_2O_3)诱导人胃腺癌SGC7901细胞程序化死亡并降低c-myc基因的表达

目的：探讨Ａｓ２Ｏ３对胃腺癌ＳＧＣ７９０１细胞系的生物学效应及机制。方法：通过ＭＴＴ还原法检测Ａｓ２Ｏ３对该细胞系存活率的影响,从光学显微镜形态观察,流式细胞仪分析,ＤＮＡ凝胶电泳,细胞凋亡原位检测（ＴＵＮＥＬ）进行细胞凋亡的检测。半定量ＲＴＰＣＲ检测基因表达。结果：Ａｓ２Ｏ３处理ＳＧＣ７９０１细胞后,细胞的存活率明显降低,光学显微镜下可见到明显的凋亡细胞,流式细胞仪测定细胞周期的Ｇ１期前有亚２倍体的凋亡峰,ＤＮＡ凝胶电泳显示出典型的凋亡特征：ＤＮＡ有规律断裂形成的梯状图谱,细胞凋亡原位检测发现ＤＮＡ的断裂,并降低细胞ｃｍｙｃ基因的表达。结论：Ａｓ２Ｏ３能诱导人胃腺癌ＳＧＣ７９０１细胞程序化死亡并可能通过降低ｃｍｙｃ基因的表达。