Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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The chloroform fraction of Citrus limon leaves inhibits human gastric cancer cell proliferation via induction of apoptosis

  • Osman, Ahmed (Faculty of Advanced Convergence Technology and Science, Jeju National University) ;
  • Moon, Jeong Yong (Subtropical Horticulture Research Institute, Jeju National University) ;
  • Hyun, Ho Bong (Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University) ;
  • Kang, Hye Rim (Faculty of Advanced Convergence Technology and Science, Jeju National University) ;
  • Cho, Somi Kim (Faculty of Advanced Convergence Technology and Science, Jeju National University)
  • Received : 2016.03.09
  • Accepted : 2016.05.11
  • Published : 2016.09.30
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Abstract

Little information about the biological activities of Citrus limon (lemon) leaves has been reported, whereas the fruit of Citrus limon (lemon) has been well-documented to contain various pro-health bio-functional compounds. In the present study, the antiproliferative activities of the lemon leaves were evaluated using several cancer cell lines. From the n-hexane, chloroform, ethyl acetate, n-butanol, and water fractions of methanolic extract of the leaves, the chloroform fraction of lemon leaves (CFLL) showed the most potent antiproliferative activity in the AGS human gastric cancer cells. The current study demonstrates that CFLL induces apoptosis in AGS cells, as evidenced by an increase in apoptotic bodies, cell population in the sub-G1 phase, Bax/Bcl-2 ratio, and cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-9. Compositional analysis of the CFLL using gas chromatography mass spectrometry (GC-MS) resulted in the identification of 27 compounds including trans, trans-farnesol (3.19 %), farnesol (3.26 %), vanillic acid (1.45 %), (-)-loliolide (5.24 %) and palmitic acid (6.96 %). Understanding the modes of action of these compounds individually and/or synergistically would provide useful information about their applications in cancer prevention and therapy.

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References

  1. Chou TH, Ding HY, Hung WJ, Liang CH (2010) Antioxidative characteristics and inhibition of ${\alpha}$-melanocyte-stimulating hormone-stimulated melanogenesis of vanillin and vanillic acid from Origanum vulgare. Exp Dermatol 19: 742-750
  2. Cragg GM, Newman DJ, Snader KM (1997) Natural products in drug discovery and development. J Nat Prod 60: 52-60 https://doi.org/10.1021/np9604893
  3. da Rocha AB, Lopes RM, Schwartsmann G (2001) Natural products in anticancer therapy. Curr Opinion Pharmacol 1: 364-369 https://doi.org/10.1016/S1471-4892(01)00063-7
  4. Farnsworth NR, Akerele O, Bingel AS, Soejarto DD, Guo Z (1985) Medicinal plants in therapy. Bull World Health Organ 63: 965-981
  5. Gamet-Payrastre L, Li P, Lumeau S, Cassar G, Dupont MA, Chevolleau S, Gasc N, Tulliez J, Terce F (2000) Sulforaphane, a naturally occurring isothiocyanate, induce cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res 60: 1426-1433
  6. Gonzalez-Molina E, Dominguez-Perles R, Moreno DA, Garcia-Viguera C (2010) Natural bioactive compounds of Citrus limon for food and health. J Pharm Biomed Anal 51: 327-345 https://doi.org/10.1016/j.jpba.2009.07.027
  7. Green DR (2000) Apoptotic pathways: Paper wraps stone blunts scissors, Cell 102: 1-4 https://doi.org/10.1016/S0092-8674(00)00003-9
  8. Harada H, Yamashita U, Kurihara H, Fukushi E, Kawabata J, Kamei Y (2002) Antitumor activity of palmitic acid found as a selective cytotoxic substance in a marine red alga, Anticancer Res 22: 2587-2590
  9. Hosni K, Hassen I, M'Rabet Y, Sebei H, Casabianca H (2013) Genetic relationship between some Tunisian Citrus species based on their leaf volatile oil constituents. Biochem Syst Ecol 50: 65-71 https://doi.org/10.1016/j.bse.2013.03.035
  10. Hwang SL, Shih PH, Yen GC (2012) Neuroprotective effects of Citrus avonoids. J Agric Food Chem 60: 877-885 https://doi.org/10.1021/jf204452y
  11. Joo JH, Liao G, Collins JB, Grissom SF, Jetten AM (2007) Farnesol-induced apoptosis in human lung carcinoma cells is coupled to the endoplasmic reticulum stress response. Cancer Res 67: 7929-7936 https://doi.org/10.1158/0008-5472.CAN-07-0931
  12. Kelloff GJ, Crowell JA, Steele VE, Lubet RA, Malone WA, Boone CW, Kopelovich L, Hawk ET, Lieberman R, Lawrence JA, Ali I, Viner JL, Sigman CC (2000) Progress in cancer chemoprevention: Development of diet-derived chemopreventive agents. J Nutr 130: (Suppl. 2S) 467S-471S https://doi.org/10.1093/jn/130.2.467S
  13. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239-257 https://doi.org/10.1038/bjc.1972.33
  14. Kerr JF, Winterford CM, Harmon BV (1994) Apoptosis its significance in cancer and cancer therapy. Cancer 73: 2013-2026 https://doi.org/10.1002/1097-0142(19940415)73:8<2013::AID-CNCR2820730802>3.0.CO;2-J
  15. Kim MC, Kim SJ, Kim DS, Jeon YD, Park SJ, Lee HS, Um JY, Hong SH (2011) Vanillic acid inhibits inflammatory mediators by suppressing NFeB in lipopolysaccharide-stimulated mouse peritoneal macrophages. Immunopharm Immunot 33: 525-532 https://doi.org/10.3109/08923973.2010.547500
  16. Kim MC, Lee HJ, Lim B, Ha KT, Kim SY, So I, Kim BJ (2014) Quercetin induces apoptosis by inhibiting MAPKs and TRPM7 channels in AGS cells. Int J Mol Med 33: 1657-1663 https://doi.org/10.3892/ijmm.2014.1704
  17. Kitamura Y, Inden M, Miyamura A, Kakimura J, Taniguchi T, Shimohama S (2002) Possible involvement of both mitochondria- and endoplasmic reticulum-dependent caspase pathways in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. Neurosci Lett 333: 25-28 https://doi.org/10.1016/S0304-3940(02)00964-3
  18. Lowe SW, Lin AW (2000) Apoptosis in cancer. Carcinogenesis 21: 485-495 https://doi.org/10.1093/carcin/21.3.485
  19. Martinez-Arribas F, Nunez-Villar MJ, Lucas AR, Sanchez J, Tejerina A, Schneider J (2003) Immunofluorometric study of Bcl-2 and Bax expression in clinical fresh tumor samples from breast cancer patients. Apoptosis 12: 1543-1568
  20. Miyake Y, Yamamoto K, Morimitsu Y, Osawa T (1997) Characteristics of antioxidative flavonoid glycosides in lemon fruit. Food Sci Technol Int Tokyo 4: 48-53
  21. Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70: 461-477 https://doi.org/10.1021/np068054v
  22. Ogata S, Miyake Y, Yamamoto K, Okumura K, Taguchi H (2000) Apoptosis Induced by the flavonoid from Lemon Fruit (Citrus limon BURM.f.) and its metabolites in HL-60 Cells. Biosci Biotechnol 64: 1075-1078 https://doi.org/10.1271/bbb.64.1075
  23. Rao CV, Newmark HL, Reddy BS (2002) Chemopreventive effect of farnesol and lanosterol on colon carcinogenesis. Cancer Detect Prevent 26: 419-425 https://doi.org/10.1016/S0361-090X(02)00119-8
  24. Sawamura M (2000) Volatile components of essential oils of the Citrus genus. Recent Res Dev Agric Food Chem 4: 131-164
  25. Sporn MB, Suh N (2000) Chemoprevention of cancer. Carcinogenesis 21: 525-530 https://doi.org/10.1093/carcin/21.3.525
  26. Stewart BW, Kleihues P (2003) World Cancer Report. Lyon: IARC Press, Paris
  27. Torres IF, Bastida F, Hernandez T, Garcia C (2015) The effects of fresh and stabilized pruning wastes on the biomass, structure and activity of the soil microbial community in a semiarid climate. Appl Soil Ecol 89: 1-9 https://doi.org/10.1016/j.apsoil.2014.12.009
  28. Vekiari SA, Protopapadakis EE, Papadopoulou P, Papanicolaou D, Panou C, Vamvakias M (2002) Composition and seasonal variation of the essential oil from leaves and peel of a Cretan lemon variety. J Agric Food Chem 50: 147-153 https://doi.org/10.1021/jf001369a
  29. Wilson RM, Danishefsky SJ (2006) Small molecule natural products in the discovery of therapeutic agents: the synthesis connection. J Org Chem 71: 8329-8351 https://doi.org/10.1021/jo0610053
  30. Wilson RM, Danishefsky SJ (2007) Applications of total synthesis toward the discovery of clinically useful anticancer agents. Chem Soc Rev 36: 1207-1226 https://doi.org/10.1039/b611967k
  31. Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA (2004) Environmental and chemical carcinogenesis. Semin Cancer Biol 14: 473-486 https://doi.org/10.1016/j.semcancer.2004.06.010
  32. Wood DE, Newcomb EW (2000) Cleavage of bax enhances its cell death function. Exp Cell Res 256: 375-382 https://doi.org/10.1006/excr.2000.4859
  33. Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68: 251-306 https://doi.org/10.1016/S0074-7696(08)62312-8
  34. Yang X, Kang MC, Lee KW, Kang SM, Lee WW, Jeon YJ (2011) Antioxidant activity and cell protective effect of loliolide isolated from Sargassum ringgoldianum subsp. Coreanum. Algae 26: 201-208 https://doi.org/10.4490/algae.2011.26.2.201