DOI QR코드

DOI QR Code

N-Butanol Extract of Capparis spinosa L. Induces Apoptosis Primarily Through a Mitochondrial Pathway Involving mPTP Open, Cytochrome C Release and Caspase Activation

  • Ji, Yu-Bin (Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce) ;
  • Yu, Lei (Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce)
  • Published : 2014.11.28

Abstract

Background: Capparis spinosa L., a Uygur medicine, had been shown to have anti-tumor activity in our early experiments with an N-butanol extract (CSBE) as its active fraction. However, the mechanisms responsible for its effects are not clearly understood. Here, we report that treatment of SGC-7901 cells with CSBE resulted in dose-dependent reduction of cell viability and induction of apoptosis. Materials and Methods: To observe the inhibitory and killing effects of CSBE on SGC-7901, the SRB method was adopted, apoptosis being observed by electron microscopy. To clarify the mechanisms of apoptosis, Western blot and enzyme-labeled methods were used to examine the release of cytochrome c (Cyt c) and the activation of the caspase cascade. Results: By electron microscopy, apoptotic morphologic changes were detectable after CSBE administration. In this study, it was also demonstrated that CSBE induced apoptosis in SGC-7901 cells by inhibiting mPTP open, mitochondrial cytochrome c release, caspase-9 and caspase-3 activation. Conclusions: The findings indicated that CSBE induces aap optosis through mitochondrial pathway.

References

  1. Aghel N, Rashidi I, Mombeini A (2007). Hepatoprotective activity of Capparis spinosa root bark against CCl4 induced hepatic damage in mice. Iranian J Pharm Res, 4, 285-90.
  2. Alabsi AM, Ali R, Ali AM, et al (2013). Induction of caspase-9, biochemical assessment and morphological changes caused by apoptosis in cancer cells treated with goniothalamin extracted from Goniothalamus macrophyllus. Asian Pac J Cancer Prev, 14, 6273-80. https://doi.org/10.7314/APJCP.2013.14.11.6273
  3. Arends MJ, Wyllie AH (1993). Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol, 32, 223-54.
  4. Banjerdpongchai R, Khaw-On P (2013). Terpinen-4-ol induces autophagic and apoptotic cell death in human leukemic HL-60 cells. Asian Pac J Cancer Prev, 14, 7537-42. https://doi.org/10.7314/APJCP.2013.14.12.7537
  5. Banjerdpongchai R, Suwannachot K, Rattanapanone V, et al (2008). Ethanolic rhizome extract from Kaempferia parviflora Wall. ex. Baker inducesapoptosis in HL-60 cells. Asian Pac J Cancer Prev, 9, 595-600.
  6. Bernardi P, Vassanelli S, Veronese P, et al (1992). Modulation of the mitochondrial permeability transition pore. Effect of protons and divalent cations. J Biol Chem, 267, 2934-9
  7. Boga C, Forlani L, Calienni R, et al (2011). On the antibacterial activity of roots of Capparis spinosa L. Nat Prod Res, 4, 417-21.
  8. Chiarugi A, Moskowitz MA (2002). "PARP-1-a perpetrator of apoptotic cell death?". Sci, 297, 259-63. https://doi.org/10.1126/science.1072221
  9. Crompton M (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem J, 2, 233-49.
  10. Gadgoli, C, Mishra, SH (1999). Antihepatotoxic activity of p-methoxy benzoic acid from Capparis spinosa. J Ethnopharmacol, 66, 187-92. https://doi.org/10.1016/S0378-8741(98)00229-3
  11. Germano MP, De Pasquale, R D'Angelo, et al (2002). Evaluation of extracts and isolated fraction from Capparis spinosa L. buds as an antioxidant source. J Agric Food Chem, 27, 1168-71.
  12. Hossein G, Keshavarz M, Ahmadi S, et al (2013). Synergistic effects of PectaSol-C modified citrus pectin an inhibitor of Galectin-3 and paclitaxel on apoptosis of human SKOV-3 ovarian cancer cells. Asian Pac J Cancer Prev, 14, 7561-8. https://doi.org/10.7314/APJCP.2013.14.12.7561
  13. Huseini HF, Hasani-Rnjbar S, Nayebi N, et al (2013). Capparis spinosa L. (Caper) fruit extract in treatment of type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Complement Ther Med, 5, 447-52.
  14. Inan D, Elagoz S, Polat Z, et al (2012). Antitumoral effects of Melissa officinalis on breast cancer in vitro and in vivo. Asian Pac J Cancer Prev, 13, 2765-70. https://doi.org/10.7314/APJCP.2012.13.6.2765
  15. Issac Abraham SV, Palani A, Ramaswamy BR, et al (2011). Antiquorum sensing and antibiofilm potential of Capparis spinosa. Arch Med Res, 8, 658-68.
  16. Kerr JFR, Wyllie AH, Currie AR (1972). Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics. British J Cancer, 4, 239-57.
  17. Kluck RM, Bossy-Wetzel E, Green DR, et al (1997). The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Sci, 275, 1132-6. https://doi.org/10.1126/science.275.5303.1132
  18. Li P, Nijhawan D, Budihardjo I, et al (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91, 479-89. https://doi.org/10.1016/S0092-8674(00)80434-1
  19. Li WL, Yu L, Ji YB (2014). Study on chemical constituents of n-butanol extract of Capparis spinosa L. Asian J Chem, 26.
  20. Monks A, Scudiero D, Skehan P, et al (1991). Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Nat Cancer Inst, 83, 757-66. https://doi.org/10.1093/jnci/83.11.757
  21. Petronilli V, Miotto G, Canton M, et al (1999). Transient and long-lasting openings of the mitochondrial permeability transition pore can be monitored directly in intact cells by changes in mitochondrial calcein fluorescence. Biophys J, 76, 725-34. https://doi.org/10.1016/S0006-3495(99)77239-5
  22. Rasul A, Yu B, Yang LF, et al (2011). Induction of mitochondriamediated apoptosis in human gastric adenocarcinoma SGC-7901 cells by kuraridin and Nor-kurarinone isolated from Sophora flavescens. Asian Pac J Cancer Prev, 12, 2499-504.
  23. Searle J, Lawson TA, Abbott PJ, et al (1975). An electronmicroscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells. J Pathol, 3, 129-38.
  24. Siracusa L, Kulisic-Bilusic T, Politeo O, et al (2011). Phenolic composition and antioxidant activity of aqueous infusions from Capparis spinosa L. and Crithmum maritimum L. before and after submission to a two-step in vitro digestion model. J Agric Food Chem, 23, 12453-9.
  25. Skehan P, Storeng R, Scudiero D, et al (1990). New colorimetric cytotoxicity assay for anticancer-drug screening. J Nat Cancer Inst, 82, 1107-12. https://doi.org/10.1093/jnci/82.13.1107
  26. Thompson, CB (1995). "Apoptosis in the pathogenesis and treatment of disease". Sci, 267, 1456-62. https://doi.org/10.1126/science.7878464
  27. Tlili N, Khaldi A, Triki S, et al (2010). Phenolic compounds and vitamin antioxidants of caper (Capparis spinosa). Plant Foods Human Nutr, 3, 260-5.
  28. Wu JH, Chang FR, Hayashi KI, et al (2003). Antitumor Agents. Part 218: Cappamensin A, a new in vitro anticancer principle, from capparis sikkimensisy. Bioorg Med Chem Lett, 13, 2223-5. https://doi.org/10.1016/S0960-894X(03)00379-2
  29. Yang J, Liu X, Bhalla K, et al (1997). Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Sci, 275, 1129-32. https://doi.org/10.1126/science.275.5303.1129

Cited by

  1. In vitro analysis of the role of the mitochondrial apoptosis pathway in CSBE therapy against human gastric cancer vol.10, pp.6, 2015, https://doi.org/10.3892/etm.2015.2779
  2. Capparis spinosa Fruit Ethanol Extracts Exert Different Effects on the Maturation of Dendritic Cells vol.22, pp.1, 2017, https://doi.org/10.3390/molecules22010097
  3. Diet Therapy for Cancer Prevention and Treatment Based on Traditional Persian Medicine vol.70, pp.3, 2018, https://doi.org/10.1080/01635581.2018.1446095