BMC Complementary and Alternative Medicine | |
Anti-angiogenic potential of an ethanol extract of Annona atemoya seeds in vitro and in vivo | |
No Soo Kim1  Ok-Sun Bang2  Jin Tae Hong3  Jun Lee2  Jong-Shik Park2  Jin-Mu Yi3  | |
[1] Department of Korean Medicine Life Science and Technology, Korea University of Science and Technology, Daejeon, Republic of Korea;KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea;College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea | |
关键词: VEGF; HIF; Anticancer; Angiogenesis; Annona atemoya; | |
Others : 1086575 DOI : 10.1186/1472-6882-14-353 |
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received in 2014-06-17, accepted in 2014-09-19, 发布年份 2014 | |
【 摘 要 】
Background
Angiogenesis, which is initiated by certain tumor micro-environmental conditions and diverse protein factors, plays a pivotal role during tumor development and metastasis. Therefore, many efforts have been made to develop effective anti-angiogenic agents as anticancer therapeutics. In the current study, we investigated the anti-angiogenic potential of an ethanol extract of Annona atemoya seeds (EEAA) in vitro and in vivo.
Methods
The anti-angiogenic potential of EEAA was evaluated using various in vitro/in vivo models, including cell proliferation, migration, and tube formation by human umbilical vascular endothelial cells (HUVECs); a Matrigel plug assay; and tumor-induced angiogenesis. The expression of hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) was investigated using reverse transcription-polymerase chain reaction, immunoassays, and western blotting.
Results
EEAA was able to significantly inhibit the angiogenic properties of HUVECs in vitro as well as angiogenic factor-induced blood vessel formation in vivo. EEAA down-regulated the expression of VEGF and HIF-1alpha/2alpha at the mRNA and protein levels, respectively, in cancer cells under hypoxic conditions.
Conclusions
EEAA shows a strong anti-angiogenic potential in both in vitro and in vivo systems, and we suggest that EEAA may be a valuable herbal source for anticancer drug development.
【 授权许可】
2014 Yi et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
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20150116013054188.pdf | 1009KB | download | |
Figure 5. | 90KB | Image | download |
Figure 4. | 44KB | Image | download |
Figure 3. | 75KB | Image | download |
Figure 2. | 87KB | Image | download |
Figure 1. | 30KB | Image | download |
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【 参考文献 】
- [1]Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O: Type-2 pericytes participate in normal and tumoral angiogenesis. Am J Physiol Cell Physiol 2014, 307(1):C25-C38.
- [2]Flamme I, Frolich T, Risau W: Molecular mechanisms of vasculogenesis and embryonic angiogenesis. J Cell Physiol 1997, 173(2):206-210.
- [3]Jang YJ, Kim DS, Jeon OH, Kim DS: Saxatilin suppresses tumor-induced angiogenesis by regulating VEGF expression in NCI-H460 human lung cancer cells. J Biochem Mol Biol 2007, 40(3):439-443.
- [4]Matsunaga N, Chikaraishi Y, Shimazawa M, Yokota S, Hara H: Vaccinium myrtillus (Bilberry) extracts reduce angiogenesis in vitro and in vivo. Evid Based Complement Alternat Med: eCAM 2010, 7(1):47-56.
- [5]Papetti M, Herman IM: Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 2002, 282(5):C947-C970.
- [6]Tosetti F, Ferrari N, De Flora S, Albini A: Angioprevention’: angiogenesis is a common and key target for cancer chemopreventive agents. FASEB J 2002, 16(1):2-14.
- [7]Tandle A, Blazer DG 3rd, Libutti SK: Antiangiogenic gene therapy of cancer: recent developments. J Transl Med 2004, 2(1):22. BioMed Central Full Text
- [8]Huang TF, Yeh CH, Wu WB: Viper venom components affecting angiogenesis. Haemostasis 2001, 31(3–6):192-206.
- [9]Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285(21):1182-1186.
- [10]Seffrin RD, Shikano I, Akhtar Y, Isman MB: Effects of crude seed extracts of Annona atemoya and Annona squamosa L. against the cabbage looper, Trichoplusia ni in the laboratory and greenhouse. Crop Prot 2010, 29(1):20-24.
- [11]Tiangda CH, Gritsanapan W, Sookvanichsilp N, Limchalearn A: Anti-headlice activity of a preparation of Annona squamosa seed extract. Southeast Asian J Trop Med Public Health 2000, 31(Suppl 1):174-177.
- [12]Leatemia JA, Isman MB: Efficacy of crude seed extracts of Annona squamosa against diamondback moth, Plutella xylostella L. in the greenhouse. Int J Pest Manage 2004, 50(2):129-133.
- [13]Leatemia JA, Isman MB: Insecticidal activity of crude seed extracts of Annona spp., Lansium domesticum and Sandoricum koetjape against lepidopteran larvae. Phytoparasitica 2004, 32(1):30-37.
- [14]Chih HW, Chiu HF, Tang KS, Chang FR, Wu YC: Bullatacin, a potent antitumor annonaceous acetogenin, inhibits proliferation of human hepatocarcinoma cell line 2.2.15 by apoptosis induction. Life Sci 2001, 69(11):1321-1331.
- [15]Chiu HF, Chih TT, Hsian YM, Tseng CH, Wu MJ, Wu YC: Bullatacin, a potent antitumor Annonaceous acetogenin, induces apoptosis through a reduction of intracellular cAMP and cGMP levels in human hepatoma 2.2.15 cells. Biochem Pharmacol 2003, 65(3):319-327.
- [16]Fu LW, He LR, Liang YJ, Chen LM, Xiong HY, Yang XP, Pan QC: Experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells in nude mice by annonaceous acetogenin 89–2. Yao xue xue bao = Acta pharmaceutica Sinica 2003, 38(8):565-570.
- [17]Yi JM, Park JS, Oh SM, Lee J, Kim J, Oh DS, Bang OS, Kim NS: Ethanol extract of Gleditsia sinensis thorn suppresses angiogenesis in vitro and in vivo. BMC Complement Altern Med 2012, 12:243. BioMed Central Full Text
- [18]Keith B, Johnson RS, Simon MC: HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 2012, 12(1):9-22.
- [19]Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003, 3(10):721-732.
- [20]Harris AL: Hypoxia–a key regulatory factor in tumour growth. Nat Rev Cancer 2002, 2(1):38-47.
- [21]Kumaran G, Clamp AR, Jayson GC: Angiogenesis as a therapeutic target in cancer. Clin Med 2008, 8(4):455-458.
- [22]Zihlif M, Afifi F, Abu-Dahab R, Abdul Majid AM, Somrain H, Saleh MM, Nassar ZD, Naffa R: The antiangiogenic activities of ethanolic crude extracts of four Salvia species. BMC Complement Altern Med 2013, 13:358. BioMed Central Full Text
- [23]Risau W: Mechanisms of angiogenesis. Nature 1997, 386(6626):671-674.
- [24]Mabjeesh NJ, Post DE, Willard MT, Kaur B, Van Meir EG, Simons JW, Zhong H: Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells. Cancer Res 2002, 62(9):2478-2482.
- [25]Zundel W, Schindler C, Haas-Kogan D, Koong A, Kaper F, Chen E, Gottschalk AR, Ryan HE, Johnson RS, Jefferson AB, Stokoe D, Giaccia AJ: Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev 2000, 14(4):391-396.
- [26]Jiang BH, Jiang G, Zheng JZ, Lu Z, Hunter T, Vogt PK: Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ 2001, 12(7):363-369.
- [27]Kirkpatrick DL, Kuperus M, Dowdeswell M, Potier N, Donald LJ, Kunkel M, Berggren M, Angulo M, Powis G: Mechanisms of inhibition of the thioredoxin growth factor system by antitumor 2-imidazolyl disulfides. Biochem Pharmacol 1998, 55(7):987-994.
- [28]Welsh SJ, Williams RR, Birmingham A, Newman DJ, Kirkpatrick DL, Powis G: The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation. Mol Cancer Ther 2003, 2(3):235-243.
- [29]Chen B, Yuping S, Ni J: Rapamycin decreases survivin expression to induce NSCLC cell apoptosis under hypoxia through inhibiting HIF-1alpha induction. Mol Biol Rep 2012, 39(1):185-191.
- [30]Chun YS, Yeo EJ, Choi E, Teng CM, Bae JM, Kim MS, Park JW: Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells. Biochem Pharmacol 2001, 61(8):947-954.
- [31]Li SH, Shin DH, Chun YS, Lee MK, Kim MS, Park JW: A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}. Mol Cancer Ther 2008, 7(12):3729-3738.
- [32]Lau CK, Yang ZF, Lam CT, Tam KH, Poon RT, Fan ST: Suppression of hypoxia inducible factor-1alpha (HIF-1alpha) by YC-1 is dependent on murine double minute 2 (Mdm2). Biochem Biophys Res Commun 2006, 348(4):1443-1448.
- [33]Oh SH, Woo JK, Jin Q, Kang HJ, Jeong JW, Kim KW, Hong WK, Lee HY: Identification of novel antiangiogenic anticancer activities of deguelin targeting hypoxia-inducible factor-1 alpha. Int J Cancer 2008, 122(1):5-14.
- [34]Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL: Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 1996, 16(9):4604-4613.
- [35]Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM: Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J Biol Chem 2002, 277(33):29936-29944.
- [36]Eguchi H, Ikuta T, Tachibana T, Yoneda Y, Kawajiri K: A nuclear localization signal of human aryl hydrocarbon receptor nuclear translocator/hypoxia-inducible factor 1beta is a novel bipartite type recognized by the two components of nuclear pore-targeting complex. J Biol Chem 1997, 272(28):17640-17647.
- [37]Wang GL, Jiang BH, Rue EA, Semenza GL: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 1995, 92(12):5510-5514.
- [38]Chen Y, Xu SS, Chen JW, Wang Y, Xu HQ, Fan NB, Li X: Anti-tumor activity of Annona squamosa seeds extract containing annonaceous acetogenin compounds. J Ethnopharmacol 2012, 142(2):462-466.
- [39]Vila-Nova NS, Morais SM, Falcao MJ, Machado LK, Bevilaqua CM, Costa IR, Brasil NV, Andrade Junior HF: Leishmanicidal activity and cytotoxicity of compounds from two Annonacea species cultivated in Northeastern Brazil. Rev Soc Bras Med Trop 2011, 44(5):567-571.
- [40]Wele A, Zhang Y, Brouard JP, Pousset JL, Bodo B: Two cyclopeptides from the seeds of Annona cherimola. Phytochemistry 2005, 66(19):2376-2380.
- [41]Wu TY, Yang IH, Tsai YT, Wang JY, Shiurba R, Hsieh TJ, Chang FR, Chang WC: Isodesacetyluvaricin, an Annonaceous acetogenin, specifically inhibits gene expression of cyclooxygenase-2. J Nat Prod 2012, 75(4):572-576.
- [42]Kaidi A, Qualtrough D, Williams AC, Paraskeva C: Direct transcriptional up-regulation of cyclooxygenase-2 by hypoxia-inducible factor (HIF)-1 promotes colorectal tumor cell survival and enhances HIF-1 transcriptional activity during hypoxia. Cancer Res 2006, 66(13):6683-6691.