Displaying publications 61 - 80 of 122 in total

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  1. Sim DS, Chong KW, Nge CE, Low YY, Sim KS, Kam TS
    J Nat Prod, 2014 Nov 26;77(11):2504-12.
    PMID: 25333996 DOI: 10.1021/np500589u
    Seven new indole alkaloids (1-7) comprising four vobasine, two tacaman, and one corynanthe-tryptamine bisindole alkaloid were isolated from the stem-bark extract of a Malayan Tabernaemontana. Two of the new vobasine alkaloids (1, 3), as well as 16-epivobasine (15) and 16-epivobasenal (17), showed appreciable cytotoxicity toward KB cells (IC50 ca. 5 μg/mL). The structure of the known Tabernaemontana alkaloid tronoharine (8) was revised based on newly acquired NMR data, as well as X-ray diffraction analysis.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  2. Gan CY, Yoganathan K, Sim KS, Low YY, Lim SH, Kam TS
    Phytochemistry, 2014 Dec;108:234-42.
    PMID: 25442910 DOI: 10.1016/j.phytochem.2014.09.014
    Eleven indole alkaloids, comprising four corynanthean, two eburnane, one aspidofractinine, one secoleuconoxine, one andranginine, and two pauciflorine type alkaloids were isolated from the stem-bark and leaf extracts of Kopsia pauciflora. Their structures were determined using NMR and MS analyses. The catharinensine type alkaloid kopsirensine B and the secoleuconoxine alkaloid arboloscine A showed moderate to weak activity in reversing MDR in vincristine-resistant KB cells. The alkaloid content was markedly different compared to that of a sample from Malaysian Borneo.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  3. Ibrahim MY, Mohd Hashim N, Mohan S, Abdulla MA, Abdelwahab SI, Kamalidehghan B, et al.
    Drug Des Devel Ther, 2014;8:2193-211.
    PMID: 25395836 DOI: 10.2147/DDDT.S66574
    BACKGROUND: Cratoxylum arborescens has been used traditionally in Malaysia for the treatment of various ailments.

    METHODS: α-Mangostin (AM) was isolated from C. arborescens and its cell death mechanism was investigated. AM-induced cytotoxicity was observed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Acridine orange/propidium iodide staining and annexin V were used to detect cells in early phases of apoptosis. High-content screening was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release. The role of caspases-3/7, -8, and -9, reactive oxygen species, Bcl-2 and Bax expression, and cell cycle arrest were also investigated. To determine the role of the central apoptosis-related proteins, a protein array followed by immunoblot analysis was conducted. Moreover, the involvement of nuclear factor-kappa B (NF-κB) was also analyzed.

    RESULTS: Apoptosis was confirmed by the apoptotic cells stained with annexin V and increase in chromatin condensation in nucleus. Treatment of cells with AM promoted cell death-transducing signals that reduced MMP by downregulation of Bcl-2 and upregulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by the executioner caspase-3/7 and then cleaved the PARP protein. Increase of caspase-8 showed the involvement of extrinsic pathway. AM treatment significantly arrested the cells at the S phase (P<0.05) concomitant with an increase in reactive oxygen species. The protein array and Western blotting demonstrated the expression of HSP70. Moreover, AM significantly blocked the induced translocation of NF-κB from cytoplasm to nucleus.

    CONCLUSION: Together, the results demonstrate that the AM isolated from C. arborescens inhibited the proliferation of MDA-MB-231 cells, leading to cell cycle arrest and programmed cell death, which was suggested to occur through both the extrinsic and intrinsic apoptosis pathways with involvement of the NF-κB and HSP70 signaling pathways.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  4. Ahmat N, Wibowo A, Mohamad SA, Low AL, Sufian AS, Yusof MI, et al.
    J Asian Nat Prod Res, 2014;16(11):1099-107.
    PMID: 25034352 DOI: 10.1080/10286020.2014.938059
    A new tetramer oligostilbenoid possessing tetrahydrofuran ring, malaysianol C (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata, together with four known oligostilbenoids nepalensinol E (2), ϵ-viniferin (3), laevifonol (4), and ampelopsin F (5). The structures of isolated compounds were elucidated on the basis of spectral evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay, whereas the cytotoxic activity was tested using MTT assay. The plausible biogenetic routes of the isolated compounds are also discussed.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  5. Karimian H, Moghadamtousi SZ, Fadaeinasab M, Golbabapour S, Razavi M, Hajrezaie M, et al.
    Drug Des Devel Ther, 2014;8:1481-97.
    PMID: 25278746 DOI: 10.2147/DDDT.S68818
    Ferulago angulata is a medicinal plant that is traditionally known for its anti-inflammatory and antiulcer properties. The present study was aimed to evaluate its anticancer activity and the possible mechanism of action using MCF-7 as an in vitro model. F. angulata leaf extracts were prepared using solvents in the order of increasing polarity. As determined by MTT assay, F. angulata leaves hexane extract (FALHE) revealed the strongest cytotoxicity against MCF-7 cells with the half maximal inhibitory concentration (IC50) value of 5.3 ± 0.82 μg/mL. The acute toxicity study of FALHE provided evidence of the safety of the plant extract. Microscopic and flow cytometric analysis using annexin-V probe showed an induction of apoptosis in MCF-7 by FALHE. Treatment of MCF-7 cells with FALHE encouraged the intrinsic pathway of apoptosis, with cell death transducing signals that reduced the mitochondrial membrane potential with cytochrome c release from mitochondria to cytosol. The released cytochrome c triggered the activation of caspase-9. Meanwhile, the overexpression of caspase-8 suggested the involvement of an extrinsic pathway in the induced apoptosis at the late stage of treatment. Moreover, flow cytometric analysis showed that FALHE treatment significantly arrested MCF-7 cells in the G1 phase, which was associated with upregulation of p21 and p27 assessed by quantitative polymerase chain reaction. Immunofluorescence and the quantitative polymerase chain reaction analysis of MCF-7 cells after treatment with FALHE revealed an upregulation of Bax and a downregulation of Bcl-2 proteins. These findings proposed that FALHE suppressed the proliferation of MCF-7 cells via cell cycle arrest and the induction of apoptosis through intrinsic pathway.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  6. Ibrahim MY, Hashim NM, Mohan S, Abdulla MA, Kamalidehghan B, Ghaderian M, et al.
    Drug Des Devel Ther, 2014;8:1629-47.
    PMID: 25302018 DOI: 10.2147/DDDT.S66105
    Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 μg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cancer.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  7. Al Muqarrabun LM, Ahmat N, Aris SR, Norizan N, Shamsulrijal N, Yusof FZ, et al.
    Nat Prod Res, 2014;28(13):1003-9.
    PMID: 24697194 DOI: 10.1080/14786419.2014.903396
    A new triterpene, malaytaraxerate (1), and four known compounds, taraxerol (2), taraxerone (3), docosyl isoferulate (4) and docosanoic acid 2',3'-dihydroxypropyl ester (5), were isolated from the acetone extract of Sapium baccatum stem bark. The structures of the isolated compounds were determined using several spectroscopic methods, including UV-Vis, FT-IR, 1D and 2D NMR, and mass spectrometry. Major isolated compounds were assayed for cytotoxicity. The chemotaxonomic significance of this plant was also studied.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  8. Al Muqarrabun LM, Ahmat N, Aris SR, Shamsulrijal N, Baharum SN, Ahmad R, et al.
    Nat Prod Res, 2014;28(9):597-605.
    PMID: 24568340 DOI: 10.1080/14786419.2014.886211
    A new sesquiterpenoid, malayscaphiol (1), and three known compounds, lupeol (2), lupenone (3) and stigmasterol (4), were isolated from the methanolic extract of the stem bark of Scaphium macropodum. The structures of the isolated compounds were determined using several spectroscopic methods, including UV-vis, FT-IR, 1D and 2D NMR, and mass spectrometer. Major isolated compounds were assayed for cytotoxicity and anti-acetylcholinesterase activities. The chemotaxonomy significance of this plant was also discussed.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  9. Ahmed Hassan LE, Khadeer Ahamed MB, Abdul Majid AS, Iqbal MA, Al Suede FS, Haque RA, et al.
    PLoS One, 2014;9(6):e90806.
    PMID: 24608571 DOI: 10.1371/journal.pone.0090806
    Tephrosia apollinea is a perennial shrublet widely distributed in Africa and is known to have medicinal properties. The current study describes the bio-assay (cytotoxicity) guided isolation of (-)-pseudosemiglabrin from the aerial parts of T. apollinea. The structural and stereochemical features have been described using spectral and x-ray crystallographic techniques. The cytotoxicity of isolated compound was evaluated against nine cancer cell lines. In addition, human fibroblast was used as a model cell line for normal cells. The results showed that (-)-pseudosemiglabrin exhibited dose-dependent antiproliferative effect on most of the tested cancer cell lines. Selectively, the compound showed significant inhibitory effect on the proliferation of leukemia, prostate and breast cancer cell lines. Further studies revealed that, the compound exhibited proapoptotic phenomenon of cytotoxicity. Interestingly, the compound did not display toxicity against the normal human fibroblast. It can be concluded that (-)-pseudosemiglabrin is worthy for further investigation as a potential chemotherapeutic agent.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  10. Yap VA, Loong BJ, Ting KN, Loh SH, Yong KT, Low YY, et al.
    Phytochemistry, 2015 Jan;109:96-102.
    PMID: 25468714 DOI: 10.1016/j.phytochem.2014.10.032
    Hispidacine, an 8,4'-oxyneolignan featuring incorporation of an unusual 2-hydroxyethylamine moiety at C-7, and hispiloscine, a phenanthroindolizidine alkaloid, were isolated from the stem-bark and leaves of the Malaysian Ficus hispida Linn. Their structures were established by spectroscopic analysis. Hispidacine induced a moderate vasorelaxant activity in rat isolated aorta, while hispiloscine showed appreciable antiproliferative activities against MDA-MB-231, MCF-7, A549, HCT-116 and MRC-5 cell lines.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  11. Al Muqarrabun LM, Ahmat N
    Eur J Med Chem, 2015 Mar 6;92:514-30.
    PMID: 25599949 DOI: 10.1016/j.ejmech.2015.01.026
    The family Sterculiaceae is one of the most important families among flowering plants. Many of its members demonstrate medicinal properties and have been used for the treatment of various ailments and wounds. A wide range of compounds including alkaloids, phenyl propanoids, flavonoids, terpenoids and other types of compounds including hydrocarbons, sugars, quinones, phenolic acids, lactones, lignans, amine and amides have been isolated from several species in this family. Few studies have reported that some extracts and single compounds isolated from this family exhibited several biological activities, such as antimicrobial, anti-inflammatory, antioxidant and cytotoxic activities. The present review is an effort to provide information about the traditional uses, phytochemistry and pharmacology of species from family Sterculiaceae, and to uncover the gaps and potentials requiring further research opportunities regarding the chemistry and pharmacy of this family.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  12. Lim KH, Raja VJ, Bradshaw TD, Lim SH, Low YY, Kam TS
    J Nat Prod, 2015 May 22;78(5):1129-38.
    PMID: 25919190 DOI: 10.1021/acs.jnatprod.5b00117
    Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga-pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N(4)-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 μM), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 μM). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70-4.19 μM). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  13. Corlay N, Lecsö-Bornet M, Leborgne E, Blanchard F, Cachet X, Bignon J, et al.
    J Nat Prod, 2015 Jun 26;78(6):1348-56.
    PMID: 26034885 DOI: 10.1021/acs.jnatprod.5b00206
    A large-scale in vitro screening of tropical plants using an antibacterial assay permitted the selection of several species with significant antibacterial activities. Bioassay-guided purification of the dichloromethane extract of the leaves of the Malaysian species Vitex vestita, led to the isolation of six new labdane-type diterpenoids, namely, 12-epivitexolide A (2), vitexolides B and C (3 and 4), vitexolide E (8), and vitexolins A and B (5 and 6), along with six known compounds, vitexolides A (1) and D (7), acuminolide (9), 3β-hydroxyanticopalic acid (10), 8α-hydroxyanticopalic acid (11), and 6α-hydroxyanticopalic acid (12). Their structures were elucidated on the basis of 1D and 2D NMR analyses and HRMS experiments. Both variable-temperature NMR spectroscopic studies and chemical modifications were performed to investigate the dynamic epimerization of the γ-hydroxybutenolide moiety of compounds 1-4. Compounds were assayed against a panel of 46 Gram-positive strains. Vitexolide A (1) exhibited the most potent antibacterial activity with minimal inhibitory concentration values ranging from 6 to 96 μM, whereas compounds 2 and 6-9 showed moderate antibacterial activity. The presence of a β-hydroxyalkyl-γ-hydroxybutenolide subunit contributed significantly to antibacterial activity. Compounds 1-4 and 6-9 showed cytotoxic activities against the HCT-116 cancer cell line (1 < IC50s < 10 μM) and human fetal lung fibroblast MRC5 cell line (1 < IC50s < 10 μM for compounds 1, 2, 7, 8, and 9).
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  14. Lim CK, Subramaniam H, Say YH, Jong VY, Khaledi H, Chee CF
    Nat Prod Res, 2015;29(21):1970-7.
    PMID: 25716662 DOI: 10.1080/14786419.2015.1015020
    A new chromanone acid, namely caloteysmannic acid (1), along with three known compounds, calolongic acid (2), isocalolongic acid (3) and stigmasterol (4) were isolated from the stem bark of Calophyllum teysmannii. All these compounds were evaluated for their cytotoxic and antioxidant activities in the MTT and DPPH assays, respectively. The structure of compound 1 was determined by means of spectroscopic methods including 1D and 2D NMR experiments as well as HR-EIMS spectrometry. The stereochemical assignment of compound 1 was done based on the NMR results and X-ray crystallographic analysis. The preliminary assay results revealed that all the test compounds displayed potent inhibitory activity against HeLa cancer cell line, in particular with compound 1 which exhibited the highest cytotoxic activity comparable to the positive control used, cisplatin. However, no significant antioxidant activity was observed for all the test compounds in the DPPH radical scavenging capacity assay.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  15. Abubakar IB, Lim KH, Loh HS
    Nat Prod Res, 2015;29(22):2137-40.
    PMID: 25515603 DOI: 10.1080/14786419.2014.991927
    Tocotrienols have been reported to possess anticancer effects other than anti-inflammatory and antioxidant activities. This study explored the potential synergism of antiproliferative effects induced by individual alkaloid extracts of Ficus fistulosa, Ficus hispida and Ficus schwarzii combined with δ- and γ-tocotrienols against human brain glioblastoma (U87MG), lung adenocarcinoma (A549) and colorectal adenocarcinoma (HT-29) cells. Cell viability and morphological results demonstrated that extracts containing a mixture of alkaloids from the leaves and bark of F. schwarzii inhibited the proliferation of HT-29 cells, whereas the alkaloid extracts of F. fistulosa inhibited the proliferation of both U87MG and HT-29 cells and showed synergism in combined treatments with either δ- or γ-tocotrienol resulting in 2.2-34.7 fold of reduction in IC50 values of tocotrienols. The observed apoptotic cell characteristics in conjunction with the synergistic antiproliferative effects of Ficus species-derived alkaloids and tocotrienols assuredly warrant future investigations towards the development of a value-added chemotherapeutic regimen against cancers.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  16. Mah SH, Ee GC, Teh SS, Sukari MA
    Nat Prod Res, 2015;29(1):98-101.
    PMID: 25229947 DOI: 10.1080/14786419.2014.959949
    Extensive chromatographic isolation and purification of the extracts of the stem bark of Calophyllum inophyllum and Calophyllum soulattri have resulted in 11 xanthones. C. inophyllum gave inophinnin (1), inophinone (2), pyranojacareubin (5), rheediaxanthone A (6), macluraxanthone (7) and 4-hydroxyxanthone (8), while C. soulattri afforded soulattrin (3), phylattrin (4), caloxanthone C (9), brasixanthone B (10) and trapezifolixanthone (11). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D NMR, GC-MS, IR and UV. Cytotoxicity screening (MTT assay) carried out in vitro on all the xanthones using five human cancer cell lines indicated good activities for some of these xanthones. The structure-activity relationship study revealed that the inhibitory activities exhibited by these xanthone derivatives to be closely related to the existence and nature of the pyrano and the prenyl substituent groups on their skeleton.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  17. Moghadamtousi SZ, Fadaeinasab M, Nikzad S, Mohan G, Ali HM, Kadir HA
    Int J Mol Sci, 2015;16(7):15625-58.
    PMID: 26184167 DOI: 10.3390/ijms160715625
    Annona muricata is a member of the Annonaceae family and is a fruit tree with a long history of traditional use. A. muricata, also known as soursop, graviola and guanabana, is an evergreen plant that is mostly distributed in tropical and subtropical regions of the world. The fruits of A. muricata are extensively used to prepare syrups, candies, beverages, ice creams and shakes. A wide array of ethnomedicinal activities is contributed to different parts of A. muricata, and indigenous communities in Africa and South America extensively use this plant in their folk medicine. Numerous investigations have substantiated these activities, including anticancer, anticonvulsant, anti-arthritic, antiparasitic, antimalarial, hepatoprotective and antidiabetic activities. Phytochemical studies reveal that annonaceous acetogenins are the major constituents of A. muricata. More than 100 annonaceous acetogenins have been isolated from leaves, barks, seeds, roots and fruits of A. muricata. In view of the immense studies on A. muricata, this review strives to unite available information regarding its phytochemistry, traditional uses and biological activities.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  18. Saedi TA, Ghafourian S, Jafarlou M, Sabariah MN, Ismail P, Eusni RM, et al.
    J Biol Regul Homeost Agents, 2015 Apr-Jun;29(2):395-9.
    PMID: 26122228
    Tumor protein p53 encoded by the TP53 gene in humans is known as a cancer biomarker in patients diagnosed with cancer, and it plays an essential role in apoptosis, genomic stability, and inhibition of angiogenesis. Cancer therapies with common chemotherapy methods are effective, as known, but have some side effects. Berberis vulgaris is traditionally administrated as a cancer drug. The current research aims to evaluate p53 as a biomarker in WEHI-3 cell line and to demonstrate the Berberis vulgaris fruit crude extract (BVFCE) as a new anticancer drug. For this purpose, we evaluated the effect of BVFCE in different concentrations against WEHI-3cell line in vitro and determined the quantitative level of p53 gene in the treated WEHI-3 cells. The results demonstrated that even at only 1 mg/ml concentration of Berberis vulgaris crude extract, there was a low level of p53 biomarker expression on WEHI-3 cells in comparison with doxorubicin. Therefore, the current study suggests BVFCE as a reliable anti-leukaemic drug and candidate for anticancer therapy. However, further investigation need be carried out to confirm its efficiency in vivo.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
  19. Tan BL, Norhaizan ME, Yeap SK, Roselina K
    Eur Rev Med Pharmacol Sci, 2015;19(6):1022-9.
    PMID: 25855928
    Brewers' rice, a mixture of broken rice, rice bran, and rice germ, is a rice by-product in the rice industry. The present study was designed to investigate the in vitro cytotoxicity of the water extract of brewers' rice (WBR) against colorectal cancer (HT-29) cells.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification*
  20. Taha H, Looi CY, Arya A, Wong WF, Yap LF, Hasanpourghadi M, et al.
    PLoS One, 2015;10(5):e0126126.
    PMID: 25946039 DOI: 10.1371/journal.pone.0126126
    Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification
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