Drug Res (Stuttg) 2017; 67(09): 547-552
DOI: 10.1055/s-0043-110483
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Apoptosis and Caspase 3 Pathway Role on Anti-Proliferative Effects of Scrophulariaoxy Sepala Methanolic Extract on Caco-2 Cells

Ali Namvaran
1   Department of Pharmacology and Toxicology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
2   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
Mehdi Fazeli
1   Department of Pharmacology and Toxicology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
,
Safar Farajnia
3   Drug Applied Research Center - Tabriz University of Medical Sciences, Tabriz, Iran
,
Gholamreza Hamidian
4   Department of Basic, Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
,
Hassan Rezazadeh
2   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3   Drug Applied Research Center - Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 18 January 2017

accepted 27 April 2017

Publication Date:
19 June 2017 (online)

Abstract

Colorectal cancer is one the most important malignancies worldwide and finding new treatment option for this cancer is of high priority. Natural compounds are common source of drugs for treatment of various diseases including cancers. The aim of this study was to investigate the effects of Scrophularia oxysepala extract on Caco-2 cells and explore the possible role of caspase 3 pathway in inducing cell death in this cancer cells in compare with chemotherapy agents of cisplatin and capecitabine. The methanolic extract of Scrophularia oxysepala (SO) was prepared by drench method. The IC50 of extract, cisplatin and capecitabine on Caco-2 cells were determined by MTT assay. The effect of SO extract on caspase 3 expression and inducing apoptosis were determined using TUNEL assay and caspase 3 ELISA methods, respectively. The IC50 of SO extract, cisplatin and capecitabine were 300, 195 and 80 µg/ml, respectively. Analysis for apoptosis revealed that SO methanolic extract increased apoptosis significantly (P<0.001) compared with control group. The effect of high doses of SO extract on apoptosis induction were comparable to cisplatin but significantly were higher than capecitabine. Only high doses of SO methanolic extract showed significant effects (P<0.05) on increasing caspase 3 compared to control group. The methanolic extract of SO showed inhibitory effect on Caco-2 cells and induced apoptosis in a dose-dependent manner comparable to cisplatin and higher than capecitabine 2 commonly used chemotherapeutic agent for various cancers.

 
  • References

  • 1 Torre LA, Bray F, Siegel RL. et al. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108
  • 2 Parkin D, Whelan S, Ferlay J. et al. World health organization cancer incidence in five continents lyon. The World Health Organization and The International Agency for Research on Cancer 2002; 8: 1-771
  • 3 Boyle P, Langman JS. ABC of colorectal cancer: Epidemiology. BMJ 2000; 321: 805-808
  • 4 Hosseini BA, Pasdaran A, Kazemi T. et al. Dichloromethane fractions of Scrophularia oxysepala extract induce apoptosis in MCF-7 human breast cancer cells. Bosn J Basic Med Sci 2015; 15: 26-32
  • 5 Zhang X, Chen LX, Ouyang L. et al. Plant natural compounds: targeting pathways of autophagy as anti-cancer therapeutic agents. Cell Prolif 2012; 45: 466-476
  • 6 Tyagi A, Raina K, Gangar S. et al. Differential effect of grape seed extract against human non-small-cell lung cancer cells: the role of reactive oxygen species and apoptosis induction. Nutr Cancer 2013; 65 (Suppl. 01) 44-53
  • 7 Orangi M, Pasdaran A, Shanehbandi D. et al. Cytotoxic and apoptotic activities of methanolic subfractions of scrophularia oxysepala against human breast cancer cell line. Evid Based Complement Alternat Med 2016; 2016: 8540640
  • 8 Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod 2007; 70: 461-477
  • 9 Pasdaran A, Nahar L, Asnaashari S. et al. Gc-ms analysis, free-radical-scavenging and insecticidal activities of essential oil of scrophularia oxysepala boiss. Pharmaceutical Sciences 2013; 19: 1
  • 10 Manivannan A, Soundararajan P, Park YG et al. Chemical elicitorinduced modulation of antioxidant metabolism and enhancement of secondary metabolite accumulation in cell suspension cultures of scrophularia kakudensis franch. Int J Mol Sci 2016; 17
  • 11 Lange I, Moschny J, Tamanyan K. et al. Scrophularia orientalis extract induces calcium signaling and apoptosis in neuroblastoma cells. Int J Oncol 2016; 48: 1608-1616
  • 12 Tanideh N, Haddadi MH, Rokni-Hosseini MH. et al. The healing effect of scrophularia striata on experimental burn wounds infected to pseudomonas aeruginosa in rat. World J Plast Surg 2015; 4: 16-23
  • 13 Rostami F, Ghasemi HA, Taherpour K. Effect of Scrophularia striata and Ferulago angulata, as alternatives to virginiamycin, on growth performance, intestinal microbial population, immune response, and blood constituents of broiler chickens. Poult Sci 2015; 94: 2202-2209
  • 14 Valiyari S, Baradaran B, Delazar A. et al. Dichloromethane and methanol extracts of scrophularia oxysepala induces apoptosis in mcf-7 human breast cancer cells. Adv Pharm Bull 2012; 2: 223-231
  • 15 Sahu SC, Njoroge J, Bryce SM. et al. Flow cytometric evaluation of the contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells. J Appl Toxicol 2016; 36: 521-531
  • 16 Basson MD, Liu YW, Hanly AM. et al. Identification and comparative analysis of human colonocyte short-chain fatty acid response genes. J Gastrointest Surg 2000; 4: 501-512
  • 17 Ciccolini J, Fina F, Bezulier K. et al. Transmission of apoptosis in human colorectal tumor cells exposed to capecitabine, Xeloda, is mediated via Fas. Mol Cancer Ther 2002; 1: 923-927
  • 18 Peters WH, Roelofs HM. Biochemical characterization of resistance to mitoxantrone and adriamycin in Caco-2 human colon adenocarcinoma cells: a possible role for glutathione S-transferases. Cancer Res 1992; 52: 1886-1890
  • 19 Mahavorasirikul W, Viyanant V, Chaijaroenkul W. et al. Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro. BMC Complement Altern Med 2010; 10: 55
  • 20 GuangLie C, WeiShi G, GaiLing H. et al. Effect of Paris saponin on antitumor and immune function in U14 tumor-bearing mice. Afr J Tradit Complement Altern Med 2013; 10: 503-507
  • 21 Giessrigl B, Yazici G, Teichmann M. et al. Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers. Int J Oncol 2012; 40: 2063-2074
  • 22 Diaz AM, Abad MJ, Fernandez L. et al. Phenylpropanoid glycosides from Scrophularia scorodonia: in vitro anti-inflammatory activity. Life Sci 2004; 74: 2515-2526
  • 23 Bermejo P, Abad MJ, Diaz AM. et al. Antiviral activity of seven iridoids, three saikosaponins and one phenylpropanoid glycoside extracted from Bupleurum rigidum and Scrophularia scorodonia. Planta Med 2002; 68: 106-110
  • 24 Li J, Huang X, Du X. et al. Study of chemical composition and antimicrobial activity of leaves and roots of Scrophularia ningpoensis. Nat Prod Res 2009; 23: 775-780
  • 25 Shen X, Eichhorn T, Greten HJ. et al. Effects of scrophularia ningpoensis hemsl. on inhibition of proliferation, apoptosis induction and nf-kappab signaling of immortalized and cancer cell lines. Pharmaceuticals (Basel) 2012; 5: 189-208
  • 26 Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 2011; 30: 87
  • 27 Brown JM, Attardi LD. The role of apoptosis in cancer development and treatment response. Nat Rev Cancer 2005; 5: 231-237
  • 28 Reddivari L, Vanamala J, Chintharlapalli S. et al. Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspase-dependent and caspase-independent pathways. Carcinogenesis 2007; 28: 2227-2235
  • 29 Marzec KA, Martino-Echarri E, Irminger-Finger I. et al. BARD1 splice variants display mislocalization in breast cancer cells and can alter the apoptotic response to cisplatin. Cancer Lett 2016; 381: 149-155
  • 30 Cabrera J, Saavedra E, Del Rosario H. et al. Gardenin B-induced cell death in human leukemia cells involves multiple caspases but is independent of the generation of reactive oxygen species. Chem Biol Interact 2016; 256: 220-227
  • 31 Broker LE, Kruyt FA, Giaccone G. Cell death independent of caspases: a review. Clin Cancer Res 2005; 11: 3155-3162
  • 32 Liang Y, Yan C, Schor NF. Apoptosis in the absence of caspase 3. Oncogene 2001; 20: 6570-6578
  • 33 Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 2005; 100: 72-79
  • 34 Zhang L, Zhu T, Qian F. et al. Iridoid glycosides isolated from Scrophularia dentata Royle ex Benth. and their anti-inflammatory activity. Fitoterapia 2014; 98: 84-90
  • 35 Zhu L-J, Qiao C, Shen X-Y. et al. Iridoid glycosides from the roots of Scrophularia ningpoensis Hemsl. Chinese Chemical Letters 2014; 25: 1354-1356
  • 36 Hwang H, Kim C, Kim SM. et al. The hydrolyzed products of iridoid glycoside with beta-glucosidase treatment exert anti-proliferative effects through suppression of STAT3 activation and STAT3-regulated gene products in several human cancer cells. Pharm Biol 2012; 50: 8-17
  • 37 Li N, Di L, Gao WC. et al. Cytotoxic iridoids from the roots of Patrinia scabra. J Nat Prod 2012; 75: 1723-1728
  • 38 Kim MB, Kim C, Chung WS. et al. The hydrolysed products of iridoid glycosides can enhance imatinib mesylate-induced apoptosis in human myeloid leukaemia cells. Phytother Res 2015; 29: 434-443