Acylated Iridoids and Rhamnopyranoses from Premna odorata (Lamiaceae) as Novel Mesenchymal–Epithelial Transition Factor Receptor Inhibitors for the Control of Breast Cancer

Phytochemical investigation of Premna odorata Blanco, Lamiaceae, leaves afforded three new acylated iridoid glycosides 1–3 and two new acylated rhamnopyranoses 9 and 10, in addition to ten known compounds. The structures of the new compounds were confirmed using extensive 1D and 2D NMR analysis. Molecular modeling study suggested the potential of the acylated rhamnopyranoses to bind at the c‐Met kinase domain. Cell‐free Z′‐LYTE? assay testing revealed the good c‐Met phosphorylation inhibitory activity of 9, followed by 8, and 10, with IC₅₀ values of 2.5, 6.9, and 12.7 μM, respectively. The (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) cell proliferation assay testing against the human c‐Met expressing highly invasive MDA‐MB‐231 suggested compound 9 as the most active with IC₅₀ value of 13.3 μM. Testing of compound 9 against multiple phenotypic breast cancer cell lines including MCF‐7, BT‐474 cells, and MDA‐MB‐468 proved enhanced activity against the highly c‐Met expressing triple‐negative breast cancer cell lines. Acylated rhamnopyranoses are potential novel c‐Met inhibitors appropriate for future optimizations to control c‐Met‐dependent breast malignancies. Copyright © 2017 John Wiley & Sons, Ltd.     

Polar Constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their Cytotoxic/Cytostatic Activity

The methanol extract of the aerial parts of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) afforded 30 phenolic metabolites, belonging to the classes of phenylethanoid glycosides, flavonoids and simple phenolic compounds. The crude methanol extract as well as the secondary metabolites were screened for their cytotoxic/cytostatic effects against four human cancer cell lines, specifically HeLa, MCF‐7, FM3 and HCT‐116 and demonstrated considerable cell growth‐inhibitory activity. The differential cytotoxicity of the compounds implied possible structure‐activity relationships. Selected compounds were evaluated for their toxicity against human peripheral blood mononuclear cells, where some of them showed marginal toxic effects. The results suggest that M. thessalum produces secondary metabolites that demonstrate selective anticancer activity concomitantly with reduced toxicity on lymphocytes. The structure of such compounds can eventually lead to the development of novel pharmaceutical agents. Copyright © 2012 John Wiley & Sons, Ltd.     

Bioactivity‐guided Isolation of Cytotoxic Sesquiterpene Lactones of Gochnatia polymorpha ssp. floccosa

Phytochemical study of Gochnatia polymorpha (Less) Cabr. ssp. floccosa Cabr. trunk bark, guided by antiproliferative assays on 10 human cancer cell lines and the VERO cell line, yielded six known compounds identified as the triterpene bauerenyl acetate, the guaianolide 11α,13‐dihydrozaluzanin C and the dimeric guaianolides 10‐desoxygochnatiolide A, gochnatiolide A, 8‐hydroxi‐10‐desoxygochnatiolide A and 8‐hydroxigochnatiolide A. Extracts, fractions of extracts and isolated compounds were tested in vitro against a panel of human cancer cell lines, including U251 (glioma, CNS), UACC‐62 (melanoma), MCF‐7 (breast), NCI‐ADR/RES (drug‐resistant ovarian), 786.0 (kidney), NCI‐H460 (lung, no small cells), PC‐3 (prostate), OVCAR‐3 (ovarian), HT‐29 (colon), K562 (leukemia) and against the VERO no cancer cell line. Bauerenyl acetate was inactive, while 11α,13‐dihydrozaluzanin C showed weak activity against UACC62 and the VERO cell line. The most active compounds were 10‐desoxygochnatiolide A and gochnatiolide A, which inhibited the growth of kidney, melanoma, ovarian‐resistant and glioma cell lines with values of TGI (total growth inhibition) varying 0.21–1.09 µg/mL. This is the first report about cytotoxic activity of dimeric lactones against cell lines. Copyright © 2011 John Wiley & Sons, Ltd.     

Cytotoxic Properties of the Stem Bark of Citrus reticulata Blanco (Rutaceae)

The bioassay‐guided fractionation of the n‐hexane extract of Citrus reticulata Blanco (Rutaceae) stem bark yielded scoparone (1), xanthyletin (2), lupeol (3), β‐amyrin (4), stigmasterol (5), β‐sitosterol (6) and palmitic acid. The structures of these compounds were determined by comprehensive spectroscopic analyses, i.e., 1D and 2D NMR and EI‐MS, and by comparison with the reported data. Extracts, fractions and isolated compounds 1–6 were assessed for cytotoxicity by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐dphenyltetrazolium bromide (MTT) assay against three human cancer cell lines, i.e., human lung adenocarcinoma cell line A549, human breast adenocarcinoma cell line MCF7 and human Caucasian prostate adenocarcinoma cell line PC3. Significant activity of the n‐hexane and the dichloromethane extracts was observed against the breast cancer cell line MCF7 with IC₅₀s of 45.6 and 54.7 μg/mL, respectively. Moreover, the 70% ethyl acetate in n‐hexane chromatographic fraction showed significant activity displaying IC₅₀ values of 53.0, 52.4 and 49.1 μg/mL against the cancer cell lines A549, MCF7 and PC3, respectively. Encouragingly, an IC₅₀ of 510.0 μg/mL against the human normal prostate cell line PNT2 indicated very low toxicity and hence favourable selectivity indices for the 70% ethyl acetate in n‐hexane fraction in the range of 9.6–10.4 towards cell lines A549, MCF7 and PC3. Because compounds isolated from the above fraction only delivered IC₅₀ values in the range of 18.2–96.3, 9.2–34.1 and 7.5–97.2 μg/mL against A549, MCF7 and PC3 cell lines, respectively, synergistic action between compounds is suggested. Bioassay results valorize the anticancer effectivity of the stem bark of this plant in Cameroonian pharmacopoeia. Copyright © 2017 John Wiley & Sons, Ltd.     

Cytotoxic Impact of Costunolide Isolated from Costus speciosus on Breast Cancer via Differential Regulation of Cell Cycle—An In‐vitro and In‐silico Approach

Costunolide, a sesquiterpene lactone, is a biologically active molecule found in most of the medicinally valuable plants. The present study aims to evaluate the anticancer property of costunolide isolated from Costus speciosus against breast cancer cell lines (MCF‐7 and MDA‐MB‐231). Costunolide effectively reduced the viability of both MCF‐7 and MDA‐MB‐231 cell lines at an IC₅₀ value of 40 μM. Flow cytometric analysis revealed costunolide mediated cell cycle arrest at G2/M phase in both the cell types. Western blotting results confirmed the alterations in the expression of cell cycle regulators (cyclin D1, D3, CDK‐4, CDK‐6, p18 INK4c, p21 CIP1/Waf‐1 and p27 KIP1) and apoptosis inducers (caspase‐3 and caspase‐9) upon costunolide treatment in comparison with their expressions in normal breast cell line (MCF‐10A). Costunolide mediated downregulation of positive cell cycle regulators and upregulation of negative cell cycle regulators were related to the induction of apoptosis in cancer cells. The above results were validated with in‐silico results that predicted stable interactions between costunolide and cancer targets. Thus costunolide effectively induced breast cancer cell apoptosis targeting cell cycle regulation, and the compound can be used as an effective herbal therapeutic molecule to treat breast cancer with further explorations. Copyright © 2015 John Wiley & Sons, Ltd.     

Two New Xanthones from Hypericum sampsonii and biological activity of the isolated compounds

Phytochemical investigation of the CH₂Cl₂ extract of the aerial part of Hypericum sampsonii yielded two new prenylated xanthones, hypericumxanthone A and B, together with three known xanthones. Their structures were elucidated by analysis of physical and spectral (UV, IR, mass and NMR) data and comparison of spectroscopic data with those reported previously. All these compounds were evaluated for in vitro antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA). Two new compounds were also tested for their cytotoxicity against human breast (MCF‐7), hepatoma (HepG2), colon (HT‐29) and lung (A549) tumour cell lines. Two new compounds showed moderate antibacterial activities at minimum inhibitory concentrations (MIC) of 16 and 32 µg/mL, respectively, whereas the positive standard antibacterial drug, vancomycin, showed an MIC of 8 µg/mL. The other compounds were inactive against MRSA. In addition, hypericumxanthone B showed weak inhibitory activities against four human tumour cell lines. Copyright © 2010 John Wiley & Sons, Ltd.     

Rutin,a Quercetin Glycoside,Restores Chemosensitivity in Human Breast Cancer Cells

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate‐binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3‐O‐β‐d ‐rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB‐MDA‐231, selected as representative for triple‐negative breast cancer and (ii) MCF‐7 used as a well‐characterized model of HER2‐negative breast cancer. To assess the cytocompatibility of rutin against non‐cancer cells, primary human mammary fibroblasts were used as control and non‐target cells. In MDA‐MB‐231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24–48–72 h, and decreased the activity of the adenosine triphosphate‐binding cassette transporters, namely, P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non‐selective inhibition of P‐gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple‐negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd.     

Assessment of Cytotoxic Properties of Safranal and Nanoliposomal Safranal in Various Cancer Cell Lines

Saffron (Crocus sativus) is a widely used food additive used for its color and taste. It has been reported that saffron possesses significant in vivo and in vitro anti‐tumor activity. In the present study, anti‐tumor effects of safranal, the major aromatic compound in saffron, and its liposomal form were investigated. The role of apoptosis has also been explored in this toxicity. HeLa, MCF7 and L929 cell lines were cultured and exposed to safranal (0.01–3 mM) or liposomal safranal (0.04–0.32 mM). 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium (MTT) assay was performed to assess cytotoxicity. Apoptosis was evaluated by staining cells with propidium iodide and quantifying sub‐Gl peak by flow cytometry. MTT assay revealed a significant and concentration‐dependent cytotoxic effect of safranal on HeLa and MCF7 cell lines. Liposomal safranal showed enhanced effect compared to the safranal solution, as compared by their IC₅₀ concentrations. Flow cytometry results revealed induction of apoptosis by safranal. It might be concluded that safranal could be involved in saffron‐induced cell death in HeLa and MCF7 cells. Liposome encapsulation improved anti‐tumor effect of safranal. Safranal and particularly its liposomal form could be investigated as promising chemotherapeutic agents in cancer treatment. Copyright © 2013 John Wiley & Sons, Ltd.     

The Antioxidant and Anticancer Effects of Wild Carrot Oil Extract

Daucus carota L. ssp. carota (Apiacea) is used in traditional medicine in Lebanon and in different regions throughout the world. The present study investigates the in vitro anticancer activities of Daucus carota oil extract (DCOE) on four human cancer cell lines as well as its in vitro antioxidant activity. DCOE was extracted from the dried umbels with 50:50 acetone‐methanol. The oil extract was analyzed by gas chromatography–mass spectrometry and screened for its antioxidant properties in vitro using 1,1‐diphenyl‐2‐picryl hydrazyl free radical scavenging assay (DPPH), ferrous ion chelating assay (FIC) and the ferric reducing antioxidant power assay (FRAP). The anticancer activity of the oil extract against human colon (HT‐29, Caco‐2) and breast (MCF‐7, MDA‐MB‐231) cancer cell lines was evaluated using the trypan blue exclusion method and the WST‐1 cell proliferation assay. DCOE exhibited antioxidant activity in all assays used. The FRAP value was 164 ± 5.5 µmol FeSO₄/g, and the IC₅₀ values for DPPH and FIC assays were 2.1 ± 0.03 mg/ml and 0.43 ± 0.02 mg/ml, respectively. Also, DCOE demonstrated a significant increase in cell death and decrease in cell proliferation. The effect of DCOE on the cell lines exhibited time and dose‐dependent responses. The present study established that DCOE possesses both antioxidant and promising anticancer activities. Copyright © 2012 John Wiley & Sons, Ltd.     

Resveratrol derivatives from Commiphora africana (A. Rich.) Endl. display cytotoxicity and selectivity against several human cancer cell lines

Commiphora africana (A. Rich.) Endl. (Burseraceae) is a medicinal plant widely used in Nigerian ethnomedicine. The in vitro cytotoxicity of the stem bark extract of C. africana and isolated cytotoxic compounds was investigated. Three resveratrol derivatives: (E)‐resveratrol 3‐O‐rutinoside ( 1 ), 5‐methoxy‐(E)‐resveratrol 3‐O‐rutinoside ( 2 ), and pinostilbene ( 3 ), together with 3‐hydroxy‐5‐methoxybenzoic acid ( 4 ) were isolated from the methanol fraction of C. africana. Their structures were determined by extensive analysis of their HREIMS and NMR spectra. The cytotoxicity of the isolated compounds against four human carcinoma cells was determined using the MTT assay. Compound 1 displayed the highest antiproliferative effect on the cell lines, with IC₅₀ values of 16.80, 21.74, 17.89, and 17.44 μM, against MCF7, A549, PC3, and HepG2 human cancer cell lines, respectively. In addition, compounds 1 – 3 showed low toxicity against normal human prostate cell line, with selectivity indices greater than five across the carcinoma cells, indicating that the compounds possess potential in the development of low‐toxicity chemotherapeutic agents. These results support the traditional use of this plant in the treatment of cancer.     

Cycloartane triterpenoids from Cimicifuga yunnanensis induce apoptosis of breast cancer cells (MCF7) via p53‐dependent mitochondrial signaling pathway

The present study was carried out to investigate the antitumor activity of five cycloartane triterpenoids isolated from Cimicifuga yunnanensis on the breast cancer cell line MCF7 and its corresponding drug resistant subline R‐MCF7, including cimigenol‐3‐O‐β‐d ‐xylopyranoside (compound 1), 25‐O‐acetylcimigenol‐3‐O‐β‐d ‐xylopyranoside (compound 2), 25‐chlorodeoxycimigenol‐3‐O‐β‐d ‐xylopyranoside (compound 3), 25‐O‐acetylcimigenol‐3‐O‐α‐l ‐arabinopyranoside (compound 4) and 23‐O‐acetylcimigenol‐3‐O‐β‐d ‐xylopyranoside (compound 5). The results showed that compounds 2–5 have relatively high antitumor activity on both MCF7 and R‐MCF7 cells. The involvement of apoptosis as a major cause of cycloartane triterpenoids‐induced cell death was further confirmed. The results of RT‐PCR showed that compounds 2–5 increased the expression of p53 and bax, which led to the loss of mitochondrial potential and then resulted in the activation of caspase‐7. These findings collectively demonstrated that compounds 2–5 induced apoptosis of MCF7 via p53‐dependent mitochondrial pathway. Copyright © 2010 John Wiley & Sons, Ltd.     

Aqueous extract of clove inhibits tumor growth by inducing autophagy through AMPK/ULK pathway

Cloves (Syzygium aromaticum), a traditional Chinese medicinal herb, displays broad biological activity. In the present study, the aqueous extract of clove (AEC) was prepared, and its anticancer affects were studied. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetra‐zolium (MTS) analysis revealed that AEC was able to inhibit cancer cell growth in vitro on several cancer cell lines; the IC₅₀ is around 150 μg/ml for human pancreatic ASPC‐1 and human colon HT‐29 cancer cells. Treatment of the cancer cells with AEC also diminished the colony formation significantly in both human pancreatic ASPC‐1 cancer cells and human colon HT‐29 cancer cells. In vivo study revealed that AEC inhibited the tumor growth significantly in HT‐29 xenograft mice model. Transmission electron microscope, flow cytometry assay, and fluorescence microscope analysis confirmed that AEC is capable of inducing cell autophagy. Further study showed that AMPK/ULK pathway plays an important role in AEC‐induced autophagy in cancer cells. Analysis of AEC components was performed by liquid chromatograph mass spectrometer approach, and more than nine constitutes were identified in AEC fraction. The study provides evidence that AEC has potential to be developed as a novel anticancer agent or as an adjuvant in cancer chemotherapy.     

Antiproliferative effect of flavonoids and sesquiterpenoids from Achillea millefolium s.l. on cultured human tumour cell lines

The antiproliferative activities of n‐hexane, chloroform, aqueous‐methanol and aqueous extracts of the aerial parts of the Achillea millefolium aggregate on three human tumour cell lines were investigated by means of MTT assays. The chloroform‐soluble extract exerted high tumour cell proliferation inhibitory activities on HeLa and MCF‐7 cells, and a moderate effect on A431 cells; accordingly, it was subjected to detailed bioactivity‐guided fractionation. As a result of the multistep chromatographic purifications (VLC, CPC, PLC, gel filtration), five flavonoids (apigenin, luteolin, centaureidin, casticin and artemetin) and five sesquiterpenoids (paulitin, isopaulitin, psilostachyin C, desacetylmatricarin and sintenin) were isolated and identified by spectroscopic methods. The antiproliferative assay demonstrated that centaureidin is the most effective constituent of the aerial parts of yarrow: high cell growth inhibitory activities were observed especially on HeLa (IC₅₀ 0.0819 µm ) and MCF‐7 (IC₅₀ 0.1250 µm ) cells. Casticin and paulitin were also highly effective against all three tumour cell lines (IC₅₀ 1.286–4.76 µm ), while apigenin, luteolin and isopaulitin proved to be moderately active (IC₅₀ 6.95–32.88 µm ). Artemetin, psilostachyin C, desacetylmatricarin and sintenin did not display antiproliferative effects against these cell lines. This is the first report on the occurrence of seco‐pseudoguaianolides (paulitin, isopaulitin and psilostachyin C) in the Achillea genus. Copyright © 2008 John Wiley & Sons, Ltd.     

In vitro evaluation of the antiplasmodial activity of Dendropanax morbifera against chloroquine‐sensitive strains of Plasmodium falciparum

Dendropanax morbifera Leveille (Araliaceae) is well known in Korea traditional medicine for a variety of diseases. The methanol extract of the lower stem parts of D. morbifera was investigated for its activity against chloroquine‐sensitive strains of Plasmodium falciparum using the parasite lactate dehydrogenase assay method. Two cycloartane‐type glycosides oleifoliosides A (1) and B (2), and dendropanoxide (3), β‐amyrin (4), α‐amyrin (5) have been isolated from the stem parts of D. morbifera. All five compounds were evaluated for in vitro antiplasmodial activities as well as their cytotoxic potential on SK‐OV‐3 cancer cell lines. Compounds 2 and 3 showed notable growth inhibitory activity against chloroquine‐sensitive strains of Plasmodium falciparum with IC₅₀ values of 6.2 and 5.3 µm . This compound showed no significant cytotoxicity (IC₅₀ > 150 µm ) evaluated using SK‐OV‐3 cancer cell lines. This is the first report on the antiplasmodial activity of the compounds from D. morbifera. Copyright © 2009 John Wiley & Sons, Ltd.     

Cytotoxic activity of Secondary Metabolites from Marine‐derived Fungus Neosartorya siamensis in Human Cancer Cells

Compounds isolated from the marine sea fan‐derived fungus Neosartorya siamensis (KUFA 0017), namely, 2,4‐dihydroxy‐3‐methylacetophenon (1), chevalone C (2), nortryptoquivaline (4), tryptoquivaline H (6), tryptoquivaline F (7), fiscalin A (8), epi‐fiscalin A (9), epi‐neofiscalin A (11) and epi‐fiscalin C (13) were tested for anti‐proliferative activity by MTT assay, DNA damage induction by comet assay, and induction of cell death by nuclear condensation assay on colon HCT116, liver HepG2 and melanoma A375 cancer cell lines. Compounds 2, 4, 8, 9, 11 and 13 presented IC₅₀ values ranging from 24 to 153 μM in the selected cell lines. Cell death was induced in HCT116 by compounds 2, 4 and 8. In HepG2, compounds 4, 8, 9 and 11 were able to induce significant cell death. This induction of cell death is possibly not related to genotoxicity because none of the compounds induced significant DNA damage. These results suggest that selected compounds present an interesting anti‐proliferative activity and cell death induction, consequently showing potential (specifically epi‐fiscalin C) as future leads for chemotherapeutic agents. Further studies on mechanisms of action should ensue. Copyright © 2016 John Wiley & Sons, Ltd.     

Cytotoxic Activity and Antioxidant Capacity of Purified Lichen Metabolites: An In Vitro Study

The purpose of this study was to investigate the effects of six lichen metabolites (diffractaic acid, lobaric acid, usnic acid, vicanicin, variolaric acid, protolichesterinic acid) on proliferation, viability and reactive oxygen species (ROS) level towards three human cancer cell lines, MCF‐7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and HCT‐116 (colon carcinoma). Cells were treated with different concentrations (2.5–100 μM) of these compounds for 48 h. In this comparative study, our lichen metabolites showed various cytotoxic effects in a concentration‐dependent manner, and usnic acid was the most potent cytotoxic agent, while variolaric acid did not inhibit the proliferation of any of the three cell lines used. All tested lichen compounds did not exhibit free radical scavenging activity using the 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) assay. The lichen metabolites did not significantly increase the intracellular ROS level and did not prevent oxidative injury induced by t‐butylhydroperoxide in HeLa cells. To better clarify the mechanism(s) of cytotoxic effect induced by protolichesterinic acid in HeLa cells, we investigated apoptotic markers such as condensation and fragmentation of nuclear chromatin and activation of caspase‐3, 8 and 9. Our results revealed that the antiproliferative activity of 40 μM protolichesterinic acid in HeLa cells is related to its ability to induce programmed cell death involving caspase‐3, 8 and 9 activation. Copyright © 2012 John Wiley & Sons, Ltd.     

多伞阿魏体外抗胃癌活性筛选、细胞凋亡及周期阻滞机制

目的:研究确定新疆特色维族药多伞阿魏体外抗胃癌活性部位及其敏感胃癌细胞系,并探讨多伞阿魏诱导胃癌细胞凋亡和细胞周期阻滞情况,为其进一步在抗胃癌方面的研究、开发与应用提供实验依据。方法:采用四甲基偶氮唑盐(MTT)比色法检测不同质量浓度多伞阿魏不同提取物(挥发油,95%乙醇提取物,及其石油醚部位,三氯甲烷部位,乙酸乙酯部位,正丁醇部位,水部位)分别对5种胃癌细胞系(AGS,MKN-45,BGC-823,MGC-803,SGC-7901)的增殖抑制作用;采用Hoechst33258荧光染色法观察多伞阿魏挥发油和三氯甲烷部位对胃癌细胞AGS和SGC-7901的影响情况;并应用细胞流式仪检测多伞阿魏不同提取部位作用胃癌细胞AGS和SGC-7901的凋亡和周期阻滞影响情况。结果:与空白组比较,多伞阿魏挥发油,95%乙醇提取物,石油醚部位,三氯甲烷部位,乙酸乙酯部位对5种胃癌细胞均有不同程度的增殖抑制作用(P0.05),并呈现浓度依赖关系。挥发油对胃癌细胞AGS呈现出较强的增殖抑制作用,其半数抑制浓度(IC50)为(7.98±2.62)mg·L~(-1),三氯甲烷部位对5种胃癌细胞系均具有较好的敏感性,对胃癌细胞SGC-7901最为敏感,其IC50为(8.73±0.55)mg·L~(-1),而正丁醇部位和水部位未呈现出明显的细胞增殖抑制作用;多伞阿魏挥发油和三氯甲烷部位作用胃癌细胞AGS和SGC-7901后,细胞核被Hoechst33258染色呈亮蓝色,且随着药物浓度的增加蓝色荧光越强;流式细胞凋亡检测结果显示,多伞阿魏不同提取部位诱导胃癌细胞AGS和SGC-7901发生不同程度的凋亡(P0.05),且随着药物浓度的增加,细胞总凋亡率明显增高;流式细胞周期检测结果显示,与空白组比较,多伞阿魏挥发油使胃癌细胞AGS的周期发生明显改变,细胞休眠期/DNA复制前期(G0/G1期)细胞比例增高,DNA复制期(S期)细胞比例降低,DNA复制后期/有丝分裂期(G2/M期)比例降低(P0.05);与空白组比较,多伞阿魏三氯甲烷部位使胃癌细胞SGC-7901的周期也发生显著改变,G0/G1期细胞比例降低,S期细胞比例增高,G2/M期比例降低(P0.05)。结论:多伞阿魏挥发油对胃癌细胞AGS呈现出较强的细胞毒活性,三氯甲烷部位对5种胃癌细胞均具有较好的增殖抑制作用,尤其对胃癌细胞SGC-7901最为敏感;多伞阿魏各提取部位诱导胃癌细胞AGS和SGC-7901主要发生晚期凋亡,而多伞阿魏乙酸乙酯部位诱导胃癌细胞AGS主要发生细胞早期凋亡;多伞阿魏挥发油能够将胃癌细胞AGS阻滞于G0/G1期,阻止细胞进入S期及G2/M期;伞阿魏三氯甲烷部位将胃癌SGC-7901细胞周期阻滞于S期。研究表明多伞阿魏挥发油和三氯甲烷部位具有较好的抗胃癌活性作用,具有潜在的研究价值和开发利用空间,并为多伞阿魏体内抗胃癌及其抗胃癌机制研究提供了一定的科学依据。     

Antiproliferative effect of benzophenones and their influence on cathepsin activity

The antiproliferative activity of two prenylated benzophenones isolated from Rheedia brasiliensis, the triprenylated garciniaphenone and the tetraprenylated benzophenone 7‐epiclusianone, was investigated against human cancer cell lines. The antiproliferative activity on melanoma (UACC‐62), breast (MCF‐7), drug‐resistant breast (NCI‐ADR), lung/non‐small cells (NCI460), ovarian (OVCAR 03), prostate (PC03), kidney (786‐0), lung (NCI‐460) and tongue (CRL‐1624 and CRL‐1623) cancer cells was determined using spectrophotometric quantification of the cellular protein content. The effect of these benzophenones on the activity of cathepsins B and G was also investigated. Garciniaphenone displayed cytostatic activity in all cell lines, whereas 7‐epiclusianone showed a dose‐dependent cytotoxic effect. The IC₅₀ values for cell proliferation revealed that 7‐epiclusianone is more active than garciniaphenone against most of the cell lines. Furthermore, the antiproliferative effects demonstrated by garciniaphenone and 7‐epiclusianone were related to their cathepsin inhibiting properties. In conclusion, 7‐epiclusianone is a promising naturally occurring agent which displays multiple inhibitory effects which may be working in concert to inhibit cancer cell proliferation in vitro. The putative pathway by which 7‐epiclusianone affects cancer cell development may involve cathepsin inhibition. Copyright © 2009 John Wiley & Sons, Ltd.     

Antibiofilm phenylethanoid glycosides from Penstemon centranthifolius

Bioassay‐guided fractionation of the antibacterial ethyl acetate‐ethanol (50 : 50) extract obtained from the aerial parts of Penstemon centranthifolius led to the isolation of six phenylethanoid glycosides (1–6) and eleven iridoid glycosides (7–17). Their structures were determined on the basis of spectroscopic analysis and comparison with the literature. Among them, two phenylethanoid glycosides, 4″′‐O–acetylverbascoside (1) and verbascoside (2), were found to show significant inhibition of the formation of bacterial biofilms by Escherichia coli UTI89. Compound 1 showed 77% biofilm inhibition at 2.5 µg/mL, and compound 2 showed 60% inhibition at 5 µg/mL. Copyright © 2009 John Wiley & Sons, Ltd.