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  • 1
    Language: English
    In: Archives of Oral Biology, October 2016, Vol.70, pp.130-142
    Description: leaf extract (TSL) has been shown to have anti-tumor effects on cancer cell lines. This study aimed to investigate the chemopreventive potential and the underlying mechanism of TSL during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. One hundred hamsters were divided into control (n = 30), carcinogenic (n = 20), preventive (n = 42), and therapeutic (n = 8) groups. The animals in carcinogenic and preventive groups were administered reverse osmosis water (carcinogenic group) or TSL (1 g/kg bw) (preventive group) by gavage daily for 4 weeks, and their bilateral pouches were painted with a 0.5% DMBA solution for 4, 9, and 12 weeks. The animals in the therapeutic group were treated with DMBA for 12 weeks prior to TSL administration for 4 weeks. Expression levels of survivin, X chromosome-linked inhibitor of apoptosis (XIAP), proliferating cell nuclear antigen (PCNA), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins were analyzed by immunohistochemistry. Apoptotic activity was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method, cytochrome C, and poly (ADP-ribose) polymerase (PARP). In the preventive group, the results showed significant decreases not only in the incidences of squamous cell carcinoma (SCC) (50%) and epithelial dysplasia (62.5%) but also in the tumor number, tumor volume, tumor burden, and the severity of dysplastic lesions. The down-regulation of survivin, XIAP, PCNA, iNOS, and COX-2 proteins and the increased apoptotic activity indicated anti-proliferative and apoptosis-inducing abilities of TSL on DMBA-induced HBP carcinogenesis. The results suggested that TSL might be a promising candidate for the prevention of oral cancer.
    Keywords: Toona Sinensis ; Dmba-Carcinogenesis ; Hamster ; Chemoprevention ; Zoology ; Dentistry
    ISSN: 0003-9969
    E-ISSN: 1879-1506
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  • 2
    Language: English
    In: Integrative Cancer Therapies, September 2017, Vol.16(3), pp.397-405
    Description: Background: Osteosarcoma is a malignant bone tumor prevalent in adolescents with poor prognosis. Toona sinensis showed potent antiproliferation effect on lung, melatonin, ovary, colon, and liver cancers. However, the effects of the species on osteosarcoma cells are rarely investigated. Results: In this study, we found fraction 1 of Toona sinensis leaf (TSL-1) resulted in inhibition of cell viability in MG-63, Saos-2, and U2OS osteosarcoma cell lines, while it only caused a moderate suppressive effect on normal osteoblasts. In addition, TSL-1 significantly elevated lactate dehydrogenase leakage and induced apoptosis and necrosis in Saos-2 cells. TSL-1 increased mRNA expression of pro-apoptotic factor Bad. Most important, TSL-1 significantly suppressed Saos-2 xenograft tumor growth in nude mice by increasing caspase-3. The IC-50 of TSL-1 for the 3 tested osteosarcoma cells is around 1/9 of that for lung cancer cells. Conclusion: We demonstrated that TSL-1, a fractionated extract from TSL, caused significant cytotoxicity to osteosarcoma cells due to apoptosis. In vivo xenograft study showed that TSL-1 suppressed the growth of osteosarcoma cells at least in part by inducing apoptosis. Our results indicate that TSL-1 has potential to be a promising anti-osteosarcoma adjuvant functional plant extract.
    Keywords: Apoptosis ; Health Food ; Osteosarcoma ; Toona Sinensis ; Xenograft ; Medicine
    ISSN: 1534-7354
    E-ISSN: 1552-695X
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  • 3
    Language: English
    In: Journal of medicinal food, 2010, Vol.13(1), pp.54-61
    Description: Includes references ; p. 54-61.
    Keywords: Plant Extracts ; Xenotransplantation ; Adenocarcinoma ; Toona ; Disease Prevention ; Lungs ; Functional Foods ; Protective Effect ; Leaves ; In Vivo Studies ; Toona Sinensis
    ISSN: 1096-620X
    E-ISSN: 15577600
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  • 4
    Language: English
    In: Neuroscience Letters, 1999, Vol.262(2), pp.85-88
    Description: The relationship between the N -methyl- d -aspartate receptor (NMDAR) and the sex-specific neurotoxicity of l -glutamate on the preoptic area (POA) of neonatal rats was studied. The NMDAR were semiquantified by western blot analysis. The kinetic change of intracellular calcium and lactate dehydrogenase (LDH) efflux were monitored as rapid and delayed toxic signals, respectively. The results showed that: (1) the NMDAR expression in POA of male rat is higher than that of females; (2) the l -glutamate (500 μ M) induced a more significant elevation of intracellular calcium in neuron derived from male rat than that from female; (3) after glutamate-treatment, the LDH efflux in neuronal culture of male rat is higher than that of females. These results suggest that the quantitative difference in NMDAR between male and female rats may contribute to the sex-specific neurotoxicity of l -glutamate on the POA of neonatal rats.
    Keywords: N-Methyl- D-Aspartate Receptor ; Preoptic Area ; Sex-Specificity ; Calcium ; Medicine ; Anatomy & Physiology
    ISSN: 0304-3940
    E-ISSN: 1872-7972
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  • 5
    Language: English
    In: BMC complementary and alternative medicine, 19 March 2015, Vol.15, pp.70
    Description: The antinociceptive effect of an aqueous extract from the leaves of Toona sinensis (TS, [A. Juss., M. Roem.]) was studied using the writhing test in mice. Different extraction fractions from TS leaf extracts (TSL1 to TSL5) were administered orally 1 h before intraperitoneal injection of acetic acid. After treatment with TSL1, TSL2, TSL3, TSL4, and TSL5 at a dose of 1 g/kg, the respective writhing responses were 39.9% (P 〈 0.001), 19.9% (P 〈 0.05), 11.7% (P = 0.052), 8.1% (P = 0.188), and 11.4% (P = 0.057) lower than the control group. Mice treated with TSL1 at 1 g/kg (39.9%, P 〈 0.001), 0.3 g/kg (38.0%, P 〈 0.001), 0.1 g/kg (46.9%, P 〈 0.001), and 0.03 g/kg (31.1%, P 〈 0.001) had significantly lower writhing responses compared with control mice. A time-course experiment was performed, which involved oral administration of TSL1 (0.1 g/kg) at 0, 0.5, 1, 2, and 6 h before acetic acid intraperitoneal injection. The most effective dose of TSL1 was 0.1 g/kg orally, with the effect beginning 30 min before treatment and persisting until 6 h. This study showed that TS has anti-visceral pain properties comparable with those of rofecoxib (a cyclooxygenase-2 inhibitor) and diclofenac, which suggests promise for the treatment of intractable visceral pain in humans.
    Keywords: Meliaceae ; Phytotherapy ; Analgesics -- Pharmacology ; Anti-Inflammatory Agents, Non-Steroidal -- Therapeutic Use ; Pain -- Drug Therapy ; Plant Extracts -- Therapeutic Use
    E-ISSN: 1472-6882
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  • 6
    Language: English
    In: Kaohsiung Journal of Medical Sciences, 2010, Vol.26(2), pp.68-75
    Description: extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from leaves (TSL-1) to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose) polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.
    Keywords: Apoptosis ; Cell Cycle ; Lung Cell Carcinoma ; Toona Sinensis ; Medicine
    ISSN: 1607-551X
    E-ISSN: 2410-8650
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  • 7
    Language: English
    In: Journal of Neurophysiology, 11/2001, Vol.86(5), pp.2374-2380
    Description: The role of N-methyl-D-aspartate (NMDA) receptor in mediating the effect of testosterone exposure prenatally on neuronal apoptosis in the sexual dimorphic nucleus of the preoptic area (SDN-POA) of rats was studied. The endogenous testosterone was diminished by prenatal stress (PNS) or simulated by testosterone exposure (TE) to understand the effect of testosterone on NR sub(1) (a functional subunit protein of NMDA receptor) expression and neuronal apoptosis. To further study whether the testosterone, after being converted into estradiol, modulates NR sub(1) expression, 4-androstein-4-ol-3,17-dione (ATD; an aromatase inhibitor) was used to block the conversion of estradiol from testosterone. The expressions of the NR, mRNA and NR sub(1) subunit protein were quantified by RT-PCR and western blotting analysis, respectively. In addition, a noncompetitive antagonist of NMDA receptor, MK-801, was used to find out whether blockage of NMDA receptor affects the naturally occurring apoptosis in SDN-POA. The results showed the following. 1) Expression of perinatal NR sub(1) subunit protein in the central part of the medial preoptic area of male rats was significantly higher than that of females, especially on postnatal days 1 and 3. 2) The testosterone level of male fetuses on embryonic day 18 was significantly higher than that of females, while the testosterone level of TE females or PNS males was similar to that of intact males or intact females, respectively. 3) The apoptotic incidence of intact male rats was significantly less than that of females, and the apoptosis was stimulated by PNS in male or inhibited by TE in female. 4) The expression of NR sub(1) subunit protein could be inhibited by PNS or ATD-treatment in male, while stimulated by TE in female. 5) NR sub(1) mRNA showed no significant difference among intact male, PNS male, ATD-treated male, TE female and intact female rats. 6) The low apoptotic incidence of male rats was significantly increased when NMDA receptor was blocked by MK-801. These results suggest that testosterone, after being converted to estradiol, may prevent the SDN-POA neurons of male rats from apoptosis through enhancing the expression of NR sub(1) at the posttranscriptional level.
    Keywords: Neuroprotection ; Estradiol ; Testosterone ; Apoptosis ; N-Methyl-D-Aspartic Acid Receptors ; Sexual Dimorphism ; Preoptic Nucleus ; Mammals (Except Primates) ; Males ; Rats ; Males ; Rats;
    ISSN: 0022-3077
    E-ISSN: 1522-1598
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  • 8
    Language: English
    In: Life Sciences, 2005, Vol.76(13), pp.1473-1487
    Description: (TS), a kind of arbor, widely distributes nowadays in Asia. The leaves of TS have been used as an effective nutritious food in Chinese society for a long time. It was reported that can induce apoptosis of cancer cells, reduce plasma glucose in diabetic rats, and improve lipolysis of differentiated 3T3-L1 adipocyte and its uptake of glucose. It has also been shown that TS may increase dynamic activity of human sperm. Thus, we are interested to investigate whether has any effect on mouse Leydig cell testosterone production, which correlates to sperm activity. Primary mouse Leydig cells were purified to conduct the in vitro experiments. Different concentrations of crude were added to primary mouse Leydig cells and the testosterone production was determined. The results showed that crude TS significantly inhibited both basal and human chorionic gonadotropin (hCG)-stimulated testosterone productions in dose dependent manner, respectively ( 〈0.05). Crude TS also reduced the forskolin- and dibutyryl-cAMP (dbcAMP)-stimulated testosterone production ( 〈0.05), which indicated that crude TS might affect protein kinase A (PKA) signal transduction pathway at the site after the formation of cyclic AMP. Moreover, TS inhibited Leydig cell steroidogenesis by suppressing the activity of steroidogenic enzymes including P450 side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, 20α-hydroxylase and 17β-hydroxysteroid dehydrogenase ( 〈0.05). In summary, these results suggested that TS inhibited steroidogenesis by suppressing the cAMP-PKA signaling pathway and the activities of steroidogenic enzymes in normal mouse Leydig cells.
    Keywords: Toona Sinensis ; Leydig Cell ; Steroidogenesis ; Regulation ; Pka ; Sciences (General) ; Biology
    ISSN: 0024-3205
    E-ISSN: 1879-0631
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  • 9
    Language: English
    In: Translational Research, 2010, Vol.155(6), pp.305-314
    Description: (TS), which is also known as , belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti–LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non–small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). IC50 value was varied between these three cell lines, the least IC value was observed in TSL-1–treated H661cells. Exposure of NSCLC cells to TSL-1 caused cell-cycle arrest in subG1 phase and caused apoptosis. Moreover, TSL-1 treatment decreased the cell-cycle regulators; cyclin D1 and CDK4 proteins by up regulating p27 expression in a dose-dependent manner. Thus, the TSL-1–induced apoptosis was further confirmed by cell morphology, subG1 peak accumulation, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) cleavage, propidium iodide (PI)-Annexin-V double staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these and studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along with doublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC.
    Keywords: Medicine
    ISSN: 1931-5244
    E-ISSN: 1878-1810
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  • 10
    Language: English
    In: Journal of medicinal food, February 2010, Vol.13(1), pp.54-61
    Description: Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G(1) peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G(1) arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti-lung cancer drug.
    Keywords: Cedrela ; Adenocarcinoma -- Drug Therapy ; Antineoplastic Agents, Phytogenic -- Therapeutic Use ; Apoptosis -- Drug Effects ; Cell Proliferation -- Drug Effects ; Lung Neoplasms -- Drug Therapy ; Plant Extracts -- Therapeutic Use
    ISSN: 1096620X
    E-ISSN: 1557-7600
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