Displaying publications 141 - 160 of 269 in total

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  1. Cytotoxicity of plants from Malaysia and Thailand used traditionally to treat cancer
    Lee CC, Houghton P
    J Ethnopharmacol, 2005 Sep 14;100(3):237-43.
    PMID: 15888378
    The SRB cytotoxicity assay was used to screen extracts and isolated constituents of some traditional medicinal plants from Malaysia and Thailand against two human cancer cell lines, COR L23 lung cancer cell line and MCF7 breast cancer cell line and the non-cancer MCF5 cell line. Five out of the seven species tested, i.e. Thai Alpinia galanga, Alpinia officinarum, Cayratia japonica, Physalis minima, Tabernaemontana divaricata, exhibited interesting cytotoxicity activity and this is the first report of cytotoxicity from any Cayratia species. Following bioassay-guided fractionation, 1'-acetoxychavicol acetate (48h exposure against COR L23 cells, IC(50) 7.8 microM against MCF7 cells, IC(50) 23.9 microM) was isolated as the major cytotoxic component of the Alpinia species, physalin F as the major cytotoxic component of Physalis minima (48 h exposure against COR L23 cells IC(50) 0.4 microM against MCF7 cells, IC(50) 0.59 microM). The Malaysian Alpinia galanga showed weak activity compared with the Thai sample and this was shown to be due to the relatively high amounts of 1'-acetoxychavicol acetate present in the Thai sample.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  2. Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds
    Shanmugam MK, Lee JH, Chai EZ, Kanchi MM, Kar S, Arfuso F, et al.
    Semin Cancer Biol, 2016 10;40-41:35-47.
    PMID: 27038646 DOI: 10.1016/j.semcancer.2016.03.005
    The association between chronic inflammation and cancer development has been well documented. One of the major obstacles in cancer treatment is the persistent autocrine and paracrine activation of pro-inflammatory transcription factors such as nuclear factor-κB, signal transducer and activator of transcription 3, activator protein 1, fork head box protein M1, and hypoxia-inducible factor 1α in a wide variety of tumor cell lines and patient specimens. This, in turn, leads to an accelerated production of cellular adhesion molecules, inflammatory cytokines, chemokines, anti-apoptotic molecules, and inducible nitric oxide synthase. Numerous medicinal plant-derived compounds have made a tremendous impact in drug discovery research endeavors, and have been reported to modulate the activation of diverse oncogenic transcription factors in various tumor models. Moreover, novel therapeutic combinations of standard chemotherapeutic drugs with these agents have significantly improved patient survival by making cancer cells more susceptible to chemotherapy and radiotherapy. In this review, we critically analyze the existing literature on the modulation of diverse transcription factors by various natural compounds and provide views on new directions for accelerating the discovery of novel drug candidates derived from Mother Nature.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  3. Cyclopenta[b]benzofuran and Secodammarane Derivatives from the Stems of Aglaia stellatopilosa
    Othman N, Pan L, Mejin M, Voong JC, Chai HB, Pannell CM, et al.
    J Nat Prod, 2016 Apr 22;79(4):784-91.
    PMID: 26974604 DOI: 10.1021/acs.jnatprod.5b00810
    Four new 2,3-secodammarane triterpenoids, stellatonins A-D (3-6), together with a new 3,4-secodammarane triterpenoid, stellatonin E (7), and the known silvestrol (1), 5‴-episilvestrol (2), and β-sitosterol, were isolated from a methanol extract of the stems of Aglaia stellatopilosa through bioassay-guided fractionation. The structures of the new compounds were elucidated using spectroscopic and chemical methods. The compounds were evaluated for their cytotoxic activity against three human cancer cell lines and for their antimicrobial activity using a microtiter plate assay against a panel of Gram-positive and Gram-negative bacteria and fungi.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  4. Fulltext γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells
    Yusof KM, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ
    Molecules, 2015 Jun 03;20(6):10280-97.
    PMID: 26046324 DOI: 10.3390/molecules200610280
    Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0-150 µg/mL) and 6G (0-300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  5. Fulltext Evaluation of selected biological capacities of Baeckea frutescens
    Navanesan S, Wahab NA, Manickam S, Sim KS
    BMC Complement Altern Med, 2015;15:186.
    PMID: 26081250 DOI: 10.1186/s12906-015-0712-6
    Baeckea frutescens is a natural remedy recorded to be used in curing various health conditions. In Peninsular Malaysia, B. frutescens is found on the mountain tops, quartz ridge and sandy coasts. To our knowledge, there is only limited published literature on B. frutescens.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  6. Berberis vulgaris fruit crude extract as a novel anti-leukaemic agent
    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/pharmacology*
  7. Water extract of brewers' rice induces antiproliferation of human colorectal cancer (HT-29) cell lines via the induction of apoptosis
    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/pharmacology
  8. Ibogan, tacaman, and cytotoxic bisindole alkaloids from tabernaemontana. Cononusine, an iboga alkaloid with unusual incorporation of a pyrrolidone moiety
    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/pharmacology*
  9. Fulltext Induction of apoptosis and oxidative stress in estrogen receptor-negative breast cancer, MDA-MB231 cells, by ethanolic mango seed extract
    Abdullah AS, Mohammed AS, Rasedee A, Mirghani ME, Al-Qubaisi MS
    BMC Complement Altern Med, 2015;15:45.
    PMID: 25881293 DOI: 10.1186/s12906-015-0575-x
    In this study, the effect of mango kernel extract in the induction of apoptosis of the breast cancer (MDA-MB-231) cell line was examined. This is an attempt to discover alternatives to current therapeutic regimes in the treatment of breast cancers.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  10. Tocotrienols inhibit growth of ZR-75-1 breast cancer cells
    Nesaretnam K, Dorasamy S, Darbre PD
    Int J Food Sci Nutr, 2000;51 Suppl:S95-103.
    PMID: 11271861
    The vitamin E component of palm oil provides a rich source of tocotrienols which have been shown previously to be growth inhibitory to two human breast cancer cell lines: responsive MCF7 cells and unresponsive MDA-MB-231 cells. Data presented here shows that the tocotrienol-rich fraction (TRF) of palm oil and individual fractions (alpha, gamma and delta) can also inhibit the growth of another responsive human breast cancer cell line, ZR-75-1. At low concentrations in the absence of oestrogen tocotrienols stimulated growth of the ZR-75-1 cells, but at higher concentrations in the presence as well as in the absence of oestradiol, tocotrienols inhibited cell growth strongly. As for MCF7 cells, alpha-tocopherol had no effect on growth of the ZR-75-1 cells in either the absence or presence of oestradiol. In studying the effects of tocotrienols in combination with antioestrogens, it was found that TRF could further inhibit growth of ZR-75-1 cells in the presence of tamoxifen (10(-7) M and 10(-8) M). Individual tocotrienol fractions (alpha, gamma, delta) could inhibit growth of ZR-75-1 cells in the presence of 10(-8) M oestradiol and 10(-8) M pure antioestrogen ICI 164,384. The immature mouse uterine weight bioassay confirmed that TRF could not exert oestrogen antagonist action in vivo. These results provide evidence of wider growth-inhibitory effects of tocotrienols beyond MCF7 and MDA-MB-231 cells, and with an oestrogen-independent mechanism of action, suggest a possible clinical advantage in combining administration of tocotrienols with antioestrogen therapy.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  11. Flavonol-cinnamate cycloadducts and diamide derivatives from Aglaia laxiflora
    Xu YJ, Wu XH, Tan BK, Lai YH, Vittal JJ, Imiyabir Z, et al.
    J Nat Prod, 2000 Apr;63(4):473-6.
    PMID: 10785416
    Leaf extracts of the Malaysian plant Aglaia laxiflora provided two cytotoxic compounds, a new rocaglaol rhamnoside (1), a known rocaglaol (2), new (but inactive) flavonol-cinnamaminopyrrolidine adducts (3-6), and their probable biosynthetic precursors (7 and trimethoxyflavonol). All structures were elucidated primarily by 2D NMR spectroscopy. The structure and stereochemistry of aglaxiflorin A (3) were confirmed by single-crystal X-ray crystallography.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  12. Cytotoxic and leishmanicidal aminoglycosteroids and aminosteroids from Holarrhena curtisii
    Kam TS, Sim KM, Koyano T, Toyoshima M, Hayashi M, Komiyama K
    J Nat Prod, 1998 Nov;61(11):1332-6.
    PMID: 9834146
    The EtOH extract of the leaves of Holarrhena curtisii yielded five new steroidal alkaloids: 17-epi-holacurtine (3), 17-epi-N-demethylholacurtine (4), holacurtinol (5), 3alpha-amino-14beta-hydroxypregnan-20-one (7), and 15alpha-hydroxyholamine (8), in addition to the known compounds, holacurtine (1), N-demethylholacurtine (2), and holamine (6). All eight compounds showed significant cytotoxic and leishmanicidal activities.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  13. Antineoplastic agents. 522. Hernandia peltata (Malaysia) and Hernandia nymphaeifolia (Republic of Maldives)
    Pettit GR, Meng Y, Gearing RP, Herald DL, Pettit RK, Doubek DL, et al.
    J Nat Prod, 2004 Feb;67(2):214-20.
    PMID: 14987061
    Bioassay (P388 lymphocytic leukemia cell line and human tumor cell lines)-guided separation of the extracts prepared from the tropical and coastal trees Hernandia peltata (Malaysia) and Hernandianymphaeifolia (Republic of Maldives) led to the isolation of a new lignan designated as hernanol (1) and 12 previously known lignans: (-)-deoxypodophyllotoxin (2), deoxypicropodophyllin (3), (+)-epiaschantin (4), (+)-epieudesmin (5), praderin (6), 5'-methoxyyatein (7), podorhizol (8), deoxypodorhizone (9), bursehernin (10), kusunokinol (11), clusin (12), and (-)-maculatin (13). The oxidative cyclization (with VOF(3)) of lignans 8, 9, and 10 resulted in a new and unusual benzopyran (14), isostegane (15), and a new dibenzocyclooctadiene lactone (16), respectively. The structure and relative stereochemistry of hernanol (1) and lignans 3, 7, 8, 9, 10, 11, and 12 were determined by 1D and 2DNMR and HRMS analyses. The structures and absolute stereochemistry of structures 2, 4, 5, 6, 13, 14, 15, and 16 were unequivocally determined by single-crystal X-ray diffraction analyses. Evaluation against the murine P388 lymphocytic leukemia cell line and human tumor cell lines showed podophyllotoxin derivatives 2 and 3 to be strong cancer cell line growth inhibitors and substances 4, 5, 8, and 15 to have marginal cancer cell line inhibitory activities. Seven of the lignans and one of the synthetic modifications (14) inhibited growth of the pathogenic bacterium Neisseria gonorrhoeae.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology
  14. Differential cytotoxic activity of Quercetin on colonic cancer cells depends on ROS generation through COX-2 expression
    Raja SB, Rajendiran V, Kasinathan NK, P A, Venkatabalasubramanian S, Murali MR, et al.
    Food Chem Toxicol, 2017 Aug;106(Pt A):92-106.
    PMID: 28479391 DOI: 10.1016/j.fct.2017.05.006
    Quercetin is a bioactive compound with anti-inflammatory, antioxidant and anticancer properties. This study exemplifies the differential cytotoxic activity of Quercetin on two human colonic cancer cell lines, HT29 and HCT15. IC50 of Quercetin for HT29 and HCT15 cells were 42.5 μM and 77.4 μM, respectively. Activation of caspase-3, increased level of cytosolic cytochrome c, decreased levels of pAkt, pGSK-3β and cyclin D1 in 40 μM Quercetin treated HT29 cells alone. Though, nuclear translocation of NFkB was increased in 40 μM Quercetin treated HT29 and HCT15 cells, over expression of COX-2 was observed in 40 μM Quercetin treated HT29 cells, whereas, Quercetin treated HCT15 cells did not expressed COX-2. Increased generation of reactive oxygen species (ROS) was observed only in Quercetin treated HT29 cells, which is due to over expression of COX-2, as COX-2 silencing inhibited Quercetin induced apoptosis and ROS generation. Insilico analysis provided evidence that Quercetin could partially inhibit COX-2 enzyme by binding to subunit A which has peroxidase activity and serves as source of ROS. However, Quercetin showed minimal effect on normal intestinal epithelial cells i,e IEC-6. To conclude, differential sensitivity of two cancer cells, HT29 and HCT15, to Quercetin depends on COX-2 dependent ROS generation that induces apoptosis and inhibits cell survival.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  15. Cytotoxic xanthones isolated from Calophyllum depressinervosum and Calophyllum buxifolium with antioxidant and cytotoxic activities
    Zamakshshari NH, Ee GCL, Ismail IS, Ibrahim Z, Mah SH
    Food Chem Toxicol, 2019 Nov;133:110800.
    PMID: 31479710 DOI: 10.1016/j.fct.2019.110800
    The stem bark of Calophyllum depressinervosum and Calophyllum buxifolium were extracted and examined for their antioxidant activities, together with cytotoxicity towards human cancer cells. The methanol extract of C. depressinervosum exhibited good DPPH and NO scavenging effects. The strongest BCB inhibition and FIC effects were shown by dichloromethane and ethyl acetate extracts of both species. Overall, DPPH, FRAP and FIC assays showed strong correlation with TPC. For cytotoxicity, hexane extract of C. depressinervosum possessed the strongest anti-proliferative activities towards SNU-1 cells while the hexane extract of C. buxifolium showed the strongest activity towards LS-174T and K562 cells with the IC50 values ranging from 7 to 17 μg/mL. The purification of plant extracts afforded eight xanthones, ananixanthone (1), caloxanthone B (2), caloxanthone I (3), caloxanthone J (4) xanthochymone B (5), thwaitesixanthone (6), 1,3,5,6-tetrahydroxyxanthone (7) and dombakinaxanthone (8). All the xanthones, except 1 were reported for the first time from both Calophyllum species. The xanthones were examined for their cytotoxic effect against K562 leukemic cells. Compounds 1 and 2 showed strong cytotoxicity with the IC50 values of 2.96 and 1.23 μg/mL, respectively. The molecular binding interaction of 2 was further investigated by performing molecular docking study with promising protein receptor Src kinase.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  16. Fulltext Induction of Apoptosis and Cytotoxicity by Isothiocyanate Sulforaphene in Human Hepatocarcinoma HepG2 Cells
    Kntayya SB, Ibrahim MD, Mohd Ain N, Iori R, Ioannides C, Abdull Razis AF
    Nutrients, 2018 Jun 04;10(6).
    PMID: 29866995 DOI: 10.3390/nu10060718
    Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G₀/G₁ phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  17. Fulltext Anticancer activity of grassy Hystrix brachyura bezoar and its mechanisms of action: An in vitro and in vivo based study
    Khan AYF, Ahmed QU, Narayanamurthy V, Razali S, Asuhaimi FA, Saleh MSM, et al.
    Biomed Pharmacother, 2019 Jun;114:108841.
    PMID: 30981106 DOI: 10.1016/j.biopha.2019.108841
    Porcupine bezoar (PB) is a calcified undigested material generally found in porcupine's (Hystrix brachyura) gastrointestinal tract. The bezoar is traditionally used in South East Asia and Europe for the treatment of cancer, poisoning, dengue, typhoid, etc. However, limited scientific studies have been performed to verify its anticancer potential to substantiate its traditional claims in the treatment of cancers. Hence, this study was aimed at investigating the in vitro and in vivo anticancer properties of two grassy PB aqueous extract (PB-A and PB-B) using A375 cancer cell line and zebrafish model, respectively. This paper presents the first report on in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, migration assay, invasion assay, qPCR experimental assay and in vivo anti-angiogenesis assay using the grassy PBs. Experimental findings revealed IC50 value are 26.59 ± 1.37 μg/mL and 30.12 ± 3.25 μg/mL for PB-A and PB-B respectively. PBs showed anti-proliferative activity with no significant cytotoxic effect on normal human dermal fibroblast (NHDF). PBs were also found to induce apoptosis via intrinsic pathway and arrest cell cycle at G2/M phase. Additionally, the findings indicated its ability to debilitate migration and invasion of A375 cells. Further evaluation using embryo zebrafish model revealed LC50 = 450.0 ± 2.50 μg/mL and 58.7 ± 5.0 μg/mL for PB-A and PB-B which also exerted anti-angiogenesis effect in zebrafish. Moreover, stearic acid, ursodeoxycholic acid and pregnenolone were identified as possible metabolites that might contribute to the anticancer effect of the both PBs. Overall, this study demonstrated that PB-A and PB-B possess potential in vitro and in vivo anticancer effects which are elicited through selective cytotoxic effect, induction of apoptosis, inhibition of migration and invasion and anti-angiogenesis. This study provides scientific evidence that the porcupine bezoar do possess anti-cancer efficacy and further justifies its traditional utility. However, more experiments with higher vertebrae models are still warranted to validate its traditional claims as an anticancer agent.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  18. In vitro anticancer properties and biological evaluation of novel natural alkaloid jerantinine B
    Qazzaz ME, Raja VJ, Lim KH, Kam TS, Lee JB, Gershkovich P, et al.
    Cancer Lett, 2016 Jan 28;370(2):185-97.
    PMID: 26515390 DOI: 10.1016/j.canlet.2015.10.013
    Natural products play a pivotal role in medicine especially in the cancer arena. Many drugs that are currently used in cancer chemotherapy originated from or were inspired by nature. Jerantinine B (JB) is one of seven novel Aspidosperma indole alkaloids isolated from the leaf extract of Tabernaemontana corymbosa. Preliminary antiproliferative assays revealed that JB and JB acetate significantly inhibited growth and colony formation, accompanied by time- and dose-dependent apoptosis induction in human cancer cell lines. JB significantly arrested cells at the G2/M cell cycle phase, potently inhibiting tubulin polymerisation. Polo-like kinase 1 (PLK1; an early trigger for the G2/M transition) was also dose-dependently inhibited by JB (IC50 1.5 µM). Furthermore, JB provoked significant increases in reactive oxygen species (ROS). Annexin V+ cell populations, dose-dependent accumulation of cleaved-PARP and caspase 3/7 activation, and reduced Bcl-2 and Mcl-1 expression confirm apoptosis induction. Preclinical in silico biopharmaceutical assessment of JB calculated rapid absorption and bioavailability >70%. Doses of 8-16 mg/kg JB were predicted to maintain unbound plasma concentrations >GI50 values in mice during efficacy studies. These findings advocate continued development of JB as a potential chemotherapeutic agent.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  19. Fulltext Anticancer Potential of Damnacanthal and Nordamnacanthal from Morinda elliptica Roots on T-lymphoblastic Leukemia Cells
    Latifah SY, Gopalsamy B, Abdul Rahim R, Manaf Ali A, Haji Lajis N
    Molecules, 2021 Mar 12;26(6).
    PMID: 33808969 DOI: 10.3390/molecules26061554
    BACKGROUND: This study reports on the cytotoxic properties of nordamnacanthal and damnacanthal, isolated from roots of Morinda elliptica on T-lymphoblastic leukaemia (CEM-SS) cell lines.

    METHODS: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.

    RESULTS: Nordamnacanthal and damnacanthal at IC50 values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg2+/Ca2+-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca2+ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle.

    CONCLUSION: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.

    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
  20. Nimbolide induces apoptosis in human nasopharyngeal cancer cells
    Chien SY, Hsu CH, Lin CC, Chuang YC, Lo YS, Hsi YT, et al.
    Environ Toxicol, 2017 Aug;32(8):2085-2092.
    PMID: 28383207 DOI: 10.1002/tox.22423
    Nasopharyngeal carcinoma (NPC), a tumor arising from epithelial cells that cover the surface and line the nasopharynx, is a rare malignancy worldwide but is prevalent in certain geographical areas, such as Southern Asia (Taiwan, Hong Kong, Singapore, Malaysia, and Southern China) and North Africa. Despite advances in diagnostic techniques and improvements in treatment modalities, the prognosis of NPC remains poor. Therefore, an effective chemotherapy regimen that enhances tumor sensitivity to chemotherapeutics is urgently required. Nimbolide, derived from Azadirachta indica, has a wide range of beneficial effects, including anti-inflammatory and anticancer properties. The present study evaluated the antitumor activity of nimbolide in NPC cells and its underlying mechanisms. Our results revealed that the treatment of HONE-1 cells with nimbolide potently inhibited cell viability. Moreover, nimbolide led to cell cycle arrest, which subsequently activated caspase-3, -8, and -9 and poly (ADP-ribose) polymerase to induce cell apoptosis. Moreover, nimbolide induced Bik, Bax, and t-Bid expression in HONE-1 cells. The results indicated that nimbolide induces apoptosis through the modulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways. Nimbolide induces apoptosis in human NPC cells and is a potential chemopreventive agent against NPC proliferation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2085-2092, 2017.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*
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