The antiangiogenic activities of ethanolic crude extracts of four Salvia species

BMC Complementary and Alternative Medicine

Randa Naffa²  Zeyad D Nassar⁴  Mohanad M Saleh⁵  Hamza Somrain⁵  Amin Malik Shah Abdul Majid³  Rana Abu-Dahab¹  Fatma Afifi¹  Malek Zihlif⁵ 

[1] Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan Amman, Jordan;Department of Physiology and Biochemistry, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan;Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia;University of Queensland, School of Pharmacy, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia;Department of Pharmacology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan

关键词: Jordan;    MCF 7;    Antiangiogenesis;    Salvia syriaca;    Salvia dominica;    Salvia hormium;    Salvia triloba;   

Others  :  1220438
DOI  :  10.1186/1472-6882-13-358

 received in 2013-01-08, accepted in 2013-11-29,  发布年份 2013

【 摘 要 】

Background

Angiogenesis is one of cancer hallmarks that are required for both cancer progression and metastasis. In this study we examined the antiangiogenic properties of the ethanolic crude extracts of four Salvia species grown in Jordan.

Methods

The direct antiangiogenic activity was evaluated using various models: ex vivo rat aortic ring assay, in vitro assessment of HUVEC proliferation and migration, and in vivo CAM assay, while we used the changes in the expression of HIF-1α and VEGF in breast cancer cells (MCF 7) as an indicative for the indirect antiangiogenic activity.

Results

All four crude extracts showed a potential antiangiogenic activity in the rat aortic assay, however two species were found to be cytotoxic against Fibroblast cell line (PLF); the finding that caused the exclusion of these two extracts from further studies. Of the two remaining extracts, S. triloba showed very promising direct and indirect antiangiogenic activities. S. triloba inhibited the HUVEC proliferation with an IC₅₀ of 90 μg/mL and HUVEC migration by 82% at 150 μg/mL. Furthermore, the in vivo CAM assay also illustrated the high impact of S. triloba against the newly formed vessel in the chicken embryonic membrane. Interestingly, the S. triloba inhibited the expression of VEGF at the mRNA and protein and the HIF-1α mRNA in the MCF 7 breast cancer cells under both normoxic and hypoxic conditions.

Conclusions

Taken together, all these findings of the direct and indirect angiogenic investigations nominated S. triloba as a highly potent antiangiogenic plant that may have chemotherapeutic and/or chemoprevention potentials.

【 授权许可】

   
2013 Zihlif et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Folkman J: Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002, 29(6, Supplement 16):15-18.
• [2]Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990, 82(1):4-7.
• [3]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer Statistics, 2009. CA Cancer J Clin 2009, 59(4):225-249.
• [4]Steeg PS: Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 2006, 12(8):895-904.
• [5]Weidner N, Semple JP, Welch WR, Folkman J: Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med 1991, 324(1):1-8.
• [6]Geho DH, Bandle RW, Clair T, Liotta LA: Physiological mechanisms of tumor-cell invasion and migration. Physiology 2005, 20(3):194-200.
• [7]Weigelt B, Peterse JL, van't Veer LJ: Breast cancer metastasis: markers and models. Nat Rev Cancer 2005, 5(8):591-602.
• [8]Quesada AR, Muñoz Chápuli R, Medina MA: Anti angiogenic drugs: from bench to clinical trials. Med Res Rev 2006, 26(4):483-530.
• [9]Browder T, Folkman J, Pirie-Shepherd S: The hemostatic system as a regulator of angiogenesis. J Biol Chem 2000, 275(3):1521.
• [10]Pugh CW, Ratcliffe PJ: Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003, 9(6):677-684.
• [11]Carmeliet P, Jain RK: Angiogenesis in cancer and other diseases. Nature 2000, 407(6801):249-257.
• [12]Denekamp J: Angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br J Radiol 1993, 66(783):181.
• [13]Albini A, Noonan DM, Ferrari N: Molecular Pathways for Cancer Angioprevention. Clin Cancer Res 2007, 13(15):4320-4325.
• [14]Goren AC, Kilic T, Dirmenci T, Bilsel G: Chemotaxonomic evaluation of Turkish species of Salvia: fatty acid compositions of seed oils. Biochem Syst Ecol 2006, 34(2):160-164.
• [15]Al-Eisawi DM: List of Jordan vascular plants. Amman 1982, 152:79-182.
• [16]Lima CF, Valentao PCR, Andrade PB, Seabra RM, Fernandes-Ferreira M, Pereira-Wilson C: Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative damage. Chem Biol Interact 2007, 167(2):107-115.
• [17]González AG, Abad T, Jiménez IA, Ravelo AG, Luis Zahira Aguiar JG, San Andrés L, Plasencia M, Herrera JR, Moujir L: A first study of antibacterial activity of diterpenes isolated from some Salvia species (Lamiaceae). Biochem Syst Ecol 1989, 17(4):293-296.
• [18]Hosseinzadeh H, Haddadkhodaparast MH, Arash AR: Antinociceptive, antiinflammatory and acute toxicity effects of Salvia leriifolia Benth. Seed extract in mice and rats. Phytother Res 2003, 17(4):422-425.
• [19]Hernandez-Perez M, Rabanal RM, de la Torre MC, Rodriguez B: Analgesic, anti-inflammatory, antipyretic and haematological effects of aethiopinone, an o-naphthoquinone diterpenoid from Salvia aethiopis roots and two hemisynthetic derivatives. Planta Med 1995, 61(6):505-509.
• [20]Alarcon Aguilar F, Roman Ramos R, Flores Saenz J, Aguirre Garcia F: Investigation on the hypoglycaemic effects of extracts of four Mexican medicinal plants in normal and Alloxan diabetic mice. Phytother Res 2002, 16(4):383-386.
• [21]Liu J, Shen HM, Ong CN: Salvia miltiorrhiza inhibits cell growth and induces apoptosis in human hepatoma HepG2 cells. Cancer Lett 2000, 153(1–2):85-93.
• [22]Wu MH, Tsai WJ, Don MJ, Chen YC, Chen IS, Kuo YC: Tanshinlactone A from Salvia miltiorrhiza modulates interleukin-2 and interferon-gamma gene expression. J Ethnopharmacol 2007, 113(2):210-217.
• [23]Keshavarz M, Mostafaie A, Mansouri K, Bidmeshkipour A, Motlagh HRM, Parvaneh S: In vitro and ex vivo antiangiogenic activity of salvia officinalis. Phytother Res 2010, 24(10):1526-1531.
• [24]Brown KJ, Maynes SF, Bezos A, Maguire DJ, Ford MD, Parish CR: A novel in vitro assay for human angiogenesis. Lab Invest 1996, 75(4):539-555.
• [25]Nassar ZD, Aisha AF, Ahamed MB, Ismail Z, Abu-Salah KM, Alrokayan SA, Abdul Majid AM: Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr. Cancer Cell Int 2011, 11(1):12. BioMed Central Full Text
• [26]Nicosia RF, Lin YJ, Hazelton D, Qian X: Endogenous regulation of angiogenesis in the rat aorta model Role of vascular endothelial growth factor. Am J Pathol 1997, 151(5):1379-1386.
• [27]Liang CC, Park AY, Guan JL: In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2007, 2(2):329-333.
• [28]West DC, Burbridge MF: Three-dimensional in vitro anglogenesis in the rat aortic ring model. Methods Mol Biol 2009, 467:189-210.
• [29]Kaneda R, Toyota M, Yamashita Y, Koinuma K, Choi YL, Ota J, Kisanuki H, Ishikawa M, Takada S, Shimada K: High‒throughput screening of genome fragments bound to differentially acetylated histones. Genes Cells 2004, 9(12):1167-1174.
• [30]Sogno I, Venč R, Ferrari N, De Censi A, Imperatori A, Noonan DM, Tosetti F, Albini A: Angioprevention with fenretinide: targeting angiogenesis in prevention and therapeutic strategies. Crit Rev Oncol Hematol 2010, 75(1):2-14.
• [31]Kerbel R, Folkman J: Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2002, 2(10):727-739.
• [32]Boik J: Natural compounds in cancer therapy. LLC, Minnesota, USA: Oregon Medical Press; 2001.
• [33]Hicklin DJ, Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005, 23(5):1011.
• [34]Brown JM, Giaccia AJ: The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 1998, 58(7):1408.
• [35]Vaupel P, Kelleher DK, Höckel M: Oxygenation status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy. Semin Oncol 2001, 28(2 Suppl 8):29-35.
• [36]Sun X, Kanwar JR, Leung E, Vale M, Krissansen GW: Regression of solid tumors by engineered overexpression of von Hippel-Lindau tumor suppressor protein and antisense hypoxia-inducible factor-1alpha. Gene Ther 2003, 10(25):2081-2089.
• [37]Zhou H, Fei W, Bai Y, Zhu S, Luo E, Chen K, Hu J: RNA interference-mediated downregulation of hypoxia-inducible factor-1[alpha] inhibits angiogenesis and survival of oral squamous cell carcinoma in vitro and in vivo. Eur J Cancer Prev 2011., 2011Publish Ahead of Print: 10.1097/CEJ.1090b1013e32834dbbda
• [38]Ali-Shtayeh MS, Yaniv Z, Mahajna J: Ethnobotanical survey in the Palestinian area: a classification of the healing potential of medicinal plants. J Ethnopharmacol 2000, 73(1–2):221-232.
• [39]Abu-Irmaileh BE, Afifi FU: Herbal medicine in Jordan with special emphasis on commonly used herbs. J Ethnopharmacol 2003, 89(2–3):193-197.
• [40]Sogno I, Vannini N, Lorusso G, Cammarota R, Noonan DM, Generoso L, Sporn MB, Albini A: Anti-angiogenic activity of a novel class of chemopreventive compounds: oleanic acid terpenoids. Recent Results Cancer Res 2009, 181:209-212.
• [41]Pfeffer U, Ferrari N, Morini M, Benelli R, Noonan D, Albini A: Antiangiogenic activity of chemopreventive drugs. Int J Biol Markers 2002, 18(1):70-74.
• [42]Lamy E, Garcia-Käufer M, Prinzhorn J, Mersch-Sundermann V: Antigenotoxic action of isothiocyanate-containing mustard as determined by two cancer biomarkers in a human intervention trial. Eur J Cancer Prev 2012, 21(4):400-406.
• [43]Lorusso G, Vannini N, Sogno I, Generoso L, Garbisa S, Noonan DM, Albini A: Mechanisms of Hyperforin as an anti-angiogenic angioprevention agent. Eur J Cancer 2009, 45(8):1474-1484.