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  1. Phytochemical Studies on Goniothalamus Woodii
    Fasihuddin B.A., Laily B. Din, Zuriati Zakaria
    Sains Malaysiana, 1996;25.
    Three compounds were isolated and characterized from the roots of Goniothalamus woodii. Based on their spectroscopic data, the compounds were identified as goniothalamin, 5-acetoxygoniothalamin and goniotriol.
    Tiga sebatian telah dipisahkan dan dicamkan daripada akar Goniothalamus woodii. Berdasarkan dari data spektroskopi, sebatian telah dikenalpasti sebagai goniotalamin, 5-asetoksigoniotalamin dan goniotriol.
    Matched MeSH terms: Goniothalamus
  2. The Chemical Constituents of the Stem Bark and Roots of Goniothalamus Tomentosus (Annonaceae)
    Hasliza Yusof, Laily Din, Zuriati Zakaria, Kamarudin Mat Salleh
    Sains Malaysiana, 2004;33.
    A new species from the Goniothalamus genus, G. tomentosus, was investigated. Two alkaloids, aristololactam BII 1 and ouregidione 2 together with a stigmasterol isolated from the stem bark and roots were identified using spectroscopic techniques.
    Spesies baru daripada genus Gonitothalamus, G. tomemtosus telah dikaji. Dua sebatian alkaloid aristololaktam BII 1 dan ouregidion 2 serta stigmasterol yang dipencilkan daripada kulit batang dan akar telah ditentukan dengan menggunakan teknik spektroskopi.
    Matched MeSH terms: Goniothalamus
  3. Fulltext Anticancer properties of Malaysian herbs: a review
    Wan Afiqah Syahirah Wan Ghazalia, A’attiyyah Ab Alim, Thirumulu Ponnuraj Kannan, Nurul Asma Abdullah, Nor Azah Mohd Ali, Khairani Idah Mokhtar
    Archives of Orofacial Sciences, 2016;11(2):19-25.
    MyJurnal
    Discovery of drugs from medicinal plants continues to provide major leads against various
    pharmacological targets, particularly in cancer diseases. Hence, there are increasing demands to discover
    more therapeutic agents from various species of medicinal plants. Chemical compounds in plants are
    important for human beings due to their therapeutic properties. Goniothalamus umbrosus, Typhonium
    flagelliforme, Myrmecodia pendens, Strobilanthes crispus and Clinacanthus nutans, are among the herbal
    species, which are consumed by cancer patients in order to combat against the growth of cancer cells. The
    present review aims to highlight on the anti-cancer properties of the listed Malaysian herbs.
    Matched MeSH terms: Goniothalamus
  4. Isolation and Characterization of Styryllactone of Goniothalamus ridleyi
    Samsiah Jusoh, Laily B. Din, Zuriati Zakaria, Fasihuddin B. Ahmad
    Sains Malaysiana, 2015;44:365-370.
    Phytochemical studies were conducted on the stem bark, stem, root and fruit of Goniothalamus ridleyi (Annonaceae)
    collected at Post Brooke, Gua Musang, Kelantan, Malaysia. Extraction using organic solvent followed by extensive
    purification using standard procedure afforded an epoxystyryllactone, 5-acetoxyisogoniothalamin oxide (1) from the
    stem bark and fruit; a styryllactone, 5-acetoxygoniothalamin (2) and a styrylpyrone, dehydrogoniothalamin (3) from
    the stem and root; a styryllactone, 5-hydroxygoniothalamin (4) from the root and styrylpyrone as well as goniothalamin
    (5) from the fruit. These compounds were characterized using spectroscopic techniques.
    Matched MeSH terms: Goniothalamus
  5. Fulltext Emerging anticancer potentials of goniothalamin and its molecular mechanisms
    Seyed MA, Jantan I, Bukhari SN
    Biomed Res Int, 2014;2014:536508.
    PMID: 25247178 DOI: 10.1155/2014/536508
    The treatment of most cancers is still inadequate, despite tremendous steady progress in drug discovery and effective prevention. Nature is an attractive source of new therapeutics. Several medicinal plants and their biomarkers have been widely used for the treatment of cancer with less known scientific basis of their functioning. Although a wide array of plant derived active metabolites play a role in the prevention and treatment of cancer, more extensive scientific evaluation of their mechanisms is still required. Styryl-lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess antiproliferative activity against cancer cells. A large body of evidence suggests that this activity is associated with the induction of apoptosis in target cells. In an effort to promote further research on the genus Goniothalamus, this review offers a broad analysis of the current knowledge on Goniothalamin (GTN) or 5, 6, dihydro-6-styryl-2-pyronone (C13H12O2), a natural occurring styryl-lactone. Therefore, it includes (i) the source of GTN and other metabolites; (ii) isolation, purification, and (iii) the molecular mechanisms of actions of GTN, especially the anticancer properties, and summarizes the role of GTN which is crucial for drug design, development, and application in future for well-being of humans.
    Matched MeSH terms: Goniothalamus/chemistry*
  6. Goniolanceolatins A-H, Cytotoxic Bis-styryllactones from Goniothalamus lanceolatus
    Bihud NV, Rasol NE, Imran S, Awang K, Ahmad FB, Mai CW, et al.
    J Nat Prod, 2019 09 27;82(9):2430-2442.
    PMID: 31433181 DOI: 10.1021/acs.jnatprod.8b01067
    Eight new bis-styryllactones, goniolanceolatins A-H (1-8), possessing a rare α,β-unsaturated δ-lactone moiety with a (6S)-configuration, were isolated from the CH2Cl2 extract of the stembark and roots of Goniothalamus lanceolatus Miq., a plant endemic to Malaysia. Absolute structures were established through extensive 1D- and 2D-NMR data analysis, in combination with electronic dichroism (ECD) data. All of the isolates were evaluated for their cytotoxicity against human lung and colorectal cancer cell lines. Compounds 2 and 4 showed cytotoxicity, with IC50 values ranging from 2.3 to 4.2 μM, and were inactive toward human noncancerous lung and colorectal cells. Compounds 1, 3, 6, 7, and 8 showed moderate to weak cytotoxicity. Docking studies of compounds 2 and 4 showed that they bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids, including Lys721, Met769, Asn818, Arg157, Ile10, and Glu12.
    Matched MeSH terms: Goniothalamus/chemistry*
  7. Chemical characterization of Goniothalamus macrophyllus and Goniothalamus malayanus leaves' essential oils
    Shakri NM, Salleh WMNHW, Khamis S, Mohamad Ali NA
    Z Naturforsch C J Biosci, 2020 Nov 26;75(11-12):485-488.
    PMID: 32966236 DOI: 10.1515/znc-2020-0090
    This study was aimed to investigate the chemical compositions of the essential oils from Goniothalamus macrophyllus and Goniothalamus malayanus growing in Malaysia. The essential oils were obtained by hydrodistillation and fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Analyses of the essential oils from G. macrophyllus and G. malayanus resulted in 93.6 and 95.4% of the total oils, respectively. The major components of G. macrophyllus oil were germacrene D (25.1%), bicyclogermacrene (11.6%), α-copaene (6.9%) and δ-cadinene (6.4%), whereas in G. malayanus oil bicyclogermacrene (43.9%), germacrene D (21.1%) and β-elemene (8.4%) were the most abundant components.
    Matched MeSH terms: Goniothalamus/chemistry*
  8. Plant growth inhibitor from the Malaysian medicinal plant Goniothalamus andersonii and related species
    Takemura T, Kamo T, Ismil R, Bakar B, Wasano N, Hiradate S, et al.
    Nat Prod Commun, 2012 Sep;7(9):1197-8.
    PMID: 23074907
    A crude methanol extract of Goniothalamus andersonii J. Sinclair strongly inhibited elongation of lettuce (Lactuca sativa L.) radicles. We conducted bioassay-guided purification of G. andersonii bark extract and obtained goniothalamin as the major bioactive compound. Its EC50 values against elongation of lettuce radicles and hypocotyls were 50 and 125 micromol L(-1), respectively. Among the six species tested, timothy was the most sensitive to goniothalamin. Quantification of this compound in other Goniothalamus species suggested that the plant inhibitory activity of this genus is explainable by goniothalamin, with G. calcareus as an exception.
    Matched MeSH terms: Goniothalamus/chemistry*
  9. Goniothalamin induces cell cycle arrest and apoptosis in H400 human oral squamous cell carcinoma: A caspase-dependent mitochondrial-mediated pathway with downregulation of NF-κβ
    Li LK, Rola AS, Kaid FA, Ali AM, Alabsi AM
    Arch Oral Biol, 2016 Apr;64:28-38.
    PMID: 26752226 DOI: 10.1016/j.archoralbio.2015.12.002
    Goniothalamin is a natural occurring styryl-lactone compound isolated from Goniothalamus macrophyllus. It had been demonstrated to process promising anticancer activity on various cancer cell lines. However, little study has been carried out on oral cancer. The aim of this study was to determine the cytotoxic effects of goniothalamin against H400 oral cancer cells and its underlying molecular pathways. Results from MTT assay demonstrated that goniothalamin exhibited selective cytotoxicity as well as inhibited cells growth of H400 in dose and time-dependent manner. This was achieved primarily via apoptosis where apoptotic bodies and membrane blebbing were observed using AO/PI and DAPI/Annexin V-FITC fluorescence double staining. In order to understand the apoptosis mechanisms induced by goniothalamin, apoptosis assessment based on mitochondrial membrane potential assay and cytochrome c enzyme-linked immunosorbent assay were carried out. Results demonstrated that the depolarization of mitochondrial transmembrane potential facilitated the release of mitochondrial cytochrome c into cytosol. Caspases assays revealed the activation of initiator caspase-9 and executioner caspase-3/7 in dose-dependent manners. This form of apoptosis was closely associated with the regulation on Bcl-2 family proteins, cell cycle arrest at S phase and inhibition of NF-κβ translocation from cytoplasm to nucleus. Conclusion, goniothalamin has the potential to act as an anticancer agent against human oral squamous cell carcinoma (H400 cells).
    Matched MeSH terms: Goniothalamus
  10. Natural cyclic polypeptides as vital phytochemical constituents from seeds of selected medicinal plants
    Dahiya R, Dahiya S, Shrivastava J, Fuloria NK, Gautam H, Mourya R, et al.
    Arch Pharm (Weinheim), 2021 Feb 01.
    PMID: 33522644 DOI: 10.1002/ardp.202000446
    Cyclopolypeptides are among the most predominant biomolecules in nature, especially those derived from plant seeds. This category of compounds has gained extraordinary attention due to remarkable variety of structures and valuable biofunctions. These congeners display enormous variation in terms of both structure and function and are the most significant biomolecules due to their widespread bioproperties. The estrogenic activity, immunosuppressive activity, cytotoxicity, vasorelaxant activity, and other properties possessed by cyclic peptides from seeds of plants make these congeners attractive leads for the drug discovery process. The current study covers the important structural features, structure-activity relationship, synthesis methods, and bioproperties of plant seeds-originated bioactive peptides from Vaccaria segetalis, Linum usitatissimum, and Goniothalamus leiocarpus, which may prove vital for the development of novel therapeutics based on a peptide skeleton.
    Matched MeSH terms: Goniothalamus
  11. Fulltext PLANT CONSERVATION STATUS AND SPECIES DIVERSITY OF HUTAN LIPUR JERAM LINANG, KELANTAN
    Siti Mariam, M.N, Jivitra, B.
    UMT Journal of Undergraduate Research, 2019;1(4):37-50.
    MyJurnal
    utan Lipur Jeram Linang in Kelantan was carried out within 0.1 ha plot. All vascular plants (except lianas and epiphytes) were enumerated and identified. A total of 255 taxa representing 121 species belonging to 87 genera in 47 families were identified. Among these were 24 species endemic to Peninsular Malaysia and 47 species with medicinal values. Plants were categorized according to growth forms as follows: 67% trees, 17% shrubs, 7% palms, 6% herbs, and 3% ferns. Based on Important value index (IVI), Elateriospermum tapos, Goniothalamus umbrosus, and Monocarpia marginalis were the most dominant species whilst Rubiaceae, Arecaceae and Fabaceae were the three most diverse families. Species diversity was high based on the Shannon-Weiner index with the value of 4.38. In this study, two species from Dipterocarpaceae, which were Dipterocarpus grandiflorus and Shorea collina, were listed as Endangered (E) and Critically Endangered (CE) species respectively according to IUCN Red List. Information gained from this study showed that the forest harbored high plant diversity and endemism, so proper management is needed to protect and conserve this forest for sustainability and development.
    Matched MeSH terms: Goniothalamus
  12. Chemical constituents from the fruit peel of Goniothalamus scortechinii
    Aryanti Abdullah, Zuriati Zakaria, Fasihuddin Ahmad, Mat-Salleh K, Laily B. Din
    Sains Malaysiana, 2009;38.
    The phytochemical investigation on the fruit peel of Goniothalamus scortechinii (Selayar Raja Ubat) obtained from Gunung Stong, Kelantan has resulted in the isolation of five compounds namely pinocembrine, altholactone, goniofufurone, goniotriol and goniopypyrone. Their structures were determined by extensive ultra violet (UV), infrared (IR), nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrum (GCMS) analysis.
    Matched MeSH terms: Goniothalamus
  13. In vitro antiplasmodial and cytotoxicity activities of crude extracts and major compounds from Goniothalamus lanceolatus
    Kaharudin FA, Zohdi RM, Mukhtar SM, Sidek HM, Bihud NV, Rasol NE, et al.
    J Ethnopharmacol, 2020 May 23;254:112657.
    PMID: 32045683 DOI: 10.1016/j.jep.2020.112657
    ETHNOPHARMACOLOGICAL RELEVANCE: Malaria, a devastating infectious disease which was initially recognized as episodic fever, is caused by parasitic protozoan of the genus Plasmodium. Medicinal plants with ethnobotanical information to treat fever and/or malaria has been the key element in identifying potential plant candidates for antimalarial screening. Goniothalamus lanceolatus Miq. (Annonaceae) is used as a folk remedy, particularly to treat fever and skin diseases.

    AIM OF THE STUDY: In this context, supported with previous preliminary data of its antiplasmodial activity, this study was undertaken to determine the in vitro antiplasmodial and cytotoxicity activities of G. lanceolatus crude extracts and its major compounds.

    MATERIALS AND METHODS: The in vitro antiplasmodial activity was determined by parasite lactate dehydrogenase (pLDH) assay on chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. The cytotoxicity activity was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on hepatocellular carcinoma (HepG2) and normal liver (WRL-68) cell lines.

    RESULTS: The root methanol extract possessed potent antiplasmodial activity against both P. falciparum 3D7 and K1 strains (IC50 = 2.7 μg/ml, SI = 140; IC50 = 1.7 μg/ml, SI = 236). Apart from the DCM extract of stem bark and root that were found to be inactive (IC50 > 50 μg/ml) against 3D7 strain, all other tested crude extracts exhibited promising (5< IC50  30 µg/ml, CC50 > 10 µM, respectively), except for the hexane and DCM extracts of root, which exerted mild cytotoxicity on HepG2 cell line (IC50 

    Matched MeSH terms: Goniothalamus/chemistry*
  14. Induction of caspase-9, biochemical assessment and morphological changes caused by apoptosis in cancer cells treated with goniothalamin extracted from Goniothalamus macrophyllus
    Alabsi AM, Ali R, Ali AM, Harun H, Al-Dubai SA, Ganasegeran K, et al.
    Asian Pac J Cancer Prev, 2013;14(11):6273-80.
    PMID: 24377517
    Goniothalamin, a natural compound extracted from Goniothalamus sp. belonging to the Annonacae family, possesses anticancer properties towards several tumor cell lines. This study focused on apoptosis induction by goniothalamin (GTN) in the Hela cervical cancer cell line. Cell growth inhibition was measured by MTT assay and the IC50 value of goniothalamin was 3.2 ± 0.72 μg/ml. Morphological changes and biochemical processes associated with apoptosis were evident on phase contrast microscopy and fluorescence microscopy. DNA fragmentation, DNA damage, caspase-9 activation and a large increase in the sub-G1 and S cell cycle phases confirmed the occurrence of apoptosis in a time-dependent manner. It could be concluded that goniothalamin show a promising cytotoxicity effect against cervical cancer cells (Hela) and the cell death mode induced by goniothalamin was apoptosis.
    Matched MeSH terms: Goniothalamus/chemistry*
  15. Fulltext Antiplatelet aggregation and platelet activating factor (PAF) receptor antagonistic activities of the essential oils of five Goniothalamus species
    Moharam BA, Jantan I, Ahmad Fb, Jalil J
    Molecules, 2010 Aug;15(8):5124-38.
    PMID: 20714290 DOI: 10.3390/molecules15085124
    Nine essential oils, hydrodistilled from different parts of five Goniothalamus species (G. velutinus Airy-Shaw, G. woodii Merr., G. clemensii Ban, G. tapis Miq. and G. tapisoides Mat Salleh) were evaluated for their ability to inhibit platelet aggregation in human whole blood using an electrical impedance method and their inhibitory effects on platelet activating factor (PAF) receptor binding with rabbit platelets using 3H-PAF as a ligand. The chemical composition of the oils was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The bark oil of G. velutinus was the most effective sample as it inhibited both arachidonic acid (AA) and ADP-induced platelet aggregation with IC(50) values of 93.6 and 87.7 microg/mL, respectively. Among the studied oils, the bark oils of G. clemensii, G. woodii, G. velutinus and the root oil of G. tapis showed significant inhibitory effects on PAF receptor binding, with IC(50 )values ranging from 3.5 to 10.5 microg/mL. The strong PAF antagonistic activity of the active oils is related to their high contents of sesquiterpenes and sesquiterpenoids, and the individual components in the oils could possibly produce a synergistic effect in the overall antiplatelet activity of the oils.
    Matched MeSH terms: Goniothalamus/chemistry*
  16. Transcriptomic evaluation of plant growth inhibitory activity of goniothalamin from the Malaysian medicinal plant Goniothalamus andersonii
    Wasano N, Takemura T, Ismil R, Bakar B, Fujii Y
    Nat Prod Commun, 2015 May;10(5):725-7.
    PMID: 26058144
    Goniothalamin produced by the Malaysian medicinal plant, Goniothalamus andersonii J. Sinclair, strongly inhibits plant growth. However, its mode of action has not been characterized at the gene expression level. We conducted DNA microarray assay to analyze the changes in early gene responses of Arabidopsis thaliana seedlings. After a 6-h exposure to goniothalamin, we observed an upregulation of genes highly associated with heat response, and 22 heat shock protein (AtHSP) genes were upregulated more than 50 fold. Together with these genes, we observed upregulation of the genes related to oxidative stress and protein folding. Also, the genes related to cell wall modification and cell growth, expansin (AtEXPA) genes, were significantly downregulated. The results suggested that goniothalamin induces oxidative stresses and inhibits the expression of cell wall-associated proteins resulting in growth inhibition of Arabidopsis seedlings.
    Matched MeSH terms: Goniothalamus/chemistry*
  17. Fulltext Cytotoxic and antioxidant compounds from the stem bark of Goniothalamus tapisoides Mat Salleh
    Kim RP, Bihud V, Bin Mohamad K, Leong KH, Bin Mohamad J, Bin Ahmad F, et al.
    Molecules, 2012 Dec 21;18(1):128-39.
    PMID: 23344192 DOI: 10.3390/molecules18010128
    Eleven compounds:goniomicin A (1), goniomicin B (2), goniomicin C (3), goniomicin D (4), tapisoidin (5), goniothalamin (6), 9-deoxygoniopypyrone (7), pterodondiol (8), liriodenine (9), benzamide (10) and cinnamic acid (11), were isolated from the stem bark of Goniothalamus tapisoides. All compounds were identified by spectroscopic analysis and, for known compounds, by comparison with published data. Goniothalamin (6) exhibited mild cytotoxic activity towards a colon cancer cell line (HT-29), with an IC(50)value of 64.17 ± 5.60 µM. Goniomicin B (2) give the highest antioxidant activity in the DPPH assay among all compounds tested, with an IC(50) of 0.207 µM.
    Matched MeSH terms: Goniothalamus/chemistry*
  18. Fulltext Bioactive Compounds from the Bornean Endemic Plant Goniothalamus longistipetes
    Teo SP, Bhakta S, Stapleton P, Gibbons S
    Antibiotics (Basel), 2020 Dec 16;9(12).
    PMID: 33339285 DOI: 10.3390/antibiotics9120913
    The present study aimed to screen plants for bioactive compounds with potential antibacterial activities. In our efforts to evaluate plants from Borneo, we isolated and elucidated the structures of four natural products from the bioactive fraction of a chloroform extract of Goniothalamus longistipetes using various chromatographic and spectroscopic techniques. The bioactive compounds were identified as a known styryllactone, (+)-altholactone ((2S,3R,3aS,7aS)-3-hydroxy-2-phenyl-2,3,3a,7a-tetrahydrobenzo-5(4H)-5-one) (1), a new styryllactone, (2S,3R,3aS,7aS)-3-hydroxy-2-phenyl-2,3,3a,7a-tetrahydrobenzo-5(4H)-5-one) (2) as well as a new alkaloid, 2,6-dimethoxyisonicotinaldehyde (3) and a new alkenyl-5-hydroxyl-phenyl benzoic acid (4). 1 and 4 showed broad-spectrum anti-bacterial activities against Gram-positive and Gram-negative bacteria as well as acid-fast model selected for this study. Compound 2 only demonstrated activities against Gram-positive bacteria whilst 3 displayed selective inhibitory activities against Gram-positive bacterial strains. Additionally, their mechanisms of anti-bacterial action were also investigated. Using Mycobacterium smegmatis as a fast-growing model of tubercle bacilli, compounds 1, 2 and 4 demonstrated inhibitory activities against whole-cell drug efflux and biofilm formation; two key intrinsic mechanisms of antibiotic resistance. Interestingly, the amphiphilic compound 4 exhibited inhibitory activity against the conjugation of plasmid pKM101 in Escherichia coli using a plate conjugation assay. Plasmid conjugation is a mechanism by which Gram-positive and Gram-negative-bacteria acquire drug resistance and virulence. These results indicated that bioactive compounds isolated from Goniothalamus longistipetes can be potential candidates as 'hits' for further optimisation.
    Matched MeSH terms: Goniothalamus
  19. Goniolandrene A and B from Goniothalamus macrophyllus
    Abdullah N, Sahibul-Anwar H, Ideris S, Hasuda T, Hitotsuyanagi Y, Takeya K, et al.
    Fitoterapia, 2013 Jul;88:1-6.
    PMID: 23570840 DOI: 10.1016/j.fitote.2013.03.028
    Goniothalamus macrophyllus (Blume) Hook. f. & Thoms. is a plant widely distributed in Malaysia. The aim of this study is to identify compounds from the roots of G. macrophyllus. The ground roots were extracted with aqueous methanol and partitioned sequentially with n-hexane, chloroform and butanol. Purification from this extracts afforded six compounds with two new compounds, namely goniolandrene-A (1), -B (2). The absolute configuration of goniolandrene B (2) was established by circular dichrosim. The compounds were cytotoxic against the P388 cells with IC50 values ranging from 0.42 to 160 μM. Goniothalamin (3) exhibited the highest inhibition of 0.42 μM.
    Matched MeSH terms: Goniothalamus/chemistry*
  20. Fulltext Goniothalamin-induced oxidative stress, DNA damage and apoptosis via caspase-2 independent and Bcl-2 independent pathways in Jurkat T-cells
    Inayat-Hussain SH, Chan KM, Rajab NF, Din LB, Chow SC, Kizilors A, et al.
    Toxicol Lett, 2010 Mar 1;193(1):108-14.
    PMID: 20026395 DOI: 10.1016/j.toxlet.2009.12.010
    Goniothalamin (GTN) isolated from Goniothalamus sp. has been demonstrated to induce apoptosis in a variety of cancer cell lines including Jurkat T leukemia cells. However, the mechanism of GTN-induced apoptosis upstream of mitochondria is still poorly defined. In this study, GTN caused a decrease in GSH with an elevation of reactive oxygen species as early as 30 min and DNA damage as assessed by Comet assay. Analysis using topoisomerase II processing of supercoiled pBR 322 DNA showed that GTN caused DNA damage via a topoisomerase II-independent pathway suggesting that cellular oxidative stress may contribute to genotoxicity. A 12-fold increase of caspase-2 activity was observed in GTN-treated Jurkat cells after 4h treatment and this was confirmed using Western blotting. Although the caspase-2 inhibitor Z-VDVAD-FMK inhibited the proteolytic activity of caspase-2, apoptosis ensued confirming that caspase-2 activity was not crucial for GTN-induced apoptosis. However, GTN-induced apoptosis was completely abrogated by N-acetylcysteine further confirming the role of oxidative stress. Since cytochrome c release was observed as early as 1h without any appreciable change in Bcl-2 protein expression, we further investigated whether overexpression of Bcl-2 confers resistance in GTN-induced cytotoxicity. Using a panel of Jurkat Bcl-2 transfectants, GTN cytotoxicity was not abrogated in these cells. In conclusion, GTN induces DNA damage and oxidative stress resulting in apoptosis which is independent of both caspase-2 and Bcl-2.
    Matched MeSH terms: Goniothalamus/chemistry
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