- Volume 42 Issue 4
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Latex of Ficus carica L. Induces Apoptosis Through Caspase and Bcl-2 Family in FaDu Human Hypopharynx Squamous Carcinoma Cells
- Shin, Bo Su (Department of Oral and Maxillofacial Surgery, College of Dentistry, Chosun University) ;
- Lee, Seul Ah (Department of Oral Biochemistry, College of Dentistry, Chosun University) ;
- Moon, Sung Min (Oral Biology Research Institute, Chosun University) ;
- Han, Seul Hee (Department of Oral Biochemistry, College of Dentistry, Chosun University) ;
- Hwang, Eun Ju (Department of Oral Biochemistry, College of Dentistry, Chosun University) ;
- Kim, Su-Gwan (Oral Biology Research Institute, Chosun University) ;
- Kim, Do Kyung (Oral Biology Research Institute, Chosun University) ;
- Kim, Jin-Soo (Oral Biology Research Institute, Chosun University) ;
- Park, Bo-Ram (Department of Dental Hygiene, Chodang University) ;
- Kim, Chun Sung (Department of Oral Biochemistry, College of Dentistry, Chosun University)
- Received : 2017.11.10
- Accepted : 2017.12.01
- Published : 2017.12.31
Ficus carica L. (common fig), one of the first plants cultivated by humans, originated in the Mediterranean basin and currently grows worldwide, including southwest Asia and South Korea. It has been used as a traditional medicine for treatment of metabolic, cardiovascular, and respiratory diseases as well as hemorrhoids and skin infections. Its pharmacological properties have recently been studied in detail, but research on the anti-cancer effect of its latex has been only been studied on a limited basis on several cell lines, such prostate cancer, breast cancer, and leukemia. In this study, we investigated the anti-cancer activity of the latex of Ficus carica L.and its underlying mechanism in FaDu human hypopharynx squamous carcinoma cells. (See Ed. note above) We confirmed through SDS-PAGE analysis and gelatinolytic activity analysis that the latex of Ficus carica contains cysteine protease ficin. Our data showed that the latex inhibited cell growth in a dose-dependent manner. In addition, the latex treatment markedly induced apoptosis in FaDu cells as determined by FACS analysis, elevated expression level of cleaved caspase-9, -3 and PARP (poly (ADP-ribose) polymerase), and. increased the expression of Bax (pro-apoptotic factor) while decreasing the expression of Bcl-2 (anti-apoptotic factor). Taken together, these results suggested that latex containing the ficin inhibited cell growth and induced apoptosis by caspase and the Bcl-2 family signaling pathway in FaDu human hypopharynx squamous carcinoma cells. These findings point to the potential of latex of Ficus carica to provide a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.
Supported by : Chosun University Dental Hospital
- Sasahira T, Kirita T, Kuniyasu H. Update of molecular pathobiology in oral cancer: a review. Int J Clin Oncol. 2014;19:431-436. doi:10.1007/s10147-014-0684-4. https://doi.org/10.1007/s10147-014-0684-4
- Sugerman PB, Savage NW. Current concepts in oral cancer. Aust Dent J. 1999;44:147-156. https://doi.org/10.1111/j.1834-7819.1999.tb00216.x
- Brocklehurst PR, Baker SR, Speight PM. Oral cancer screening: What have we learnt and what is there still to achieve? Future Oncol. 2010;6:299-304. doi:10.2217/fon.09.163. https://doi.org/10.2217/fon.09.163
- Marsh D, Suchak K, Moutasim KA, Vallath S, Hopper C, Jerjes W, Upile T, Kalavrezos N, Violette SM, Weinreb PH, Chester KA, Chana JS, Marshall JF, Hart IR, Hackshaw AK, Piper K, Thomas GJ. Stromal features are predictive of disease mortality in oral cancer patients. J Pathol. 2011;223:470-481. doi:10.1002/path.2830. https://doi.org/10.1002/path.2830
- Shah JP, Gil Z. Current concepts in management of oral cancer-surgery. Oral Oncol. 2009;45:394-401. doi:10.1016/j.oraloncology.2008.05.017. https://doi.org/10.1016/j.oraloncology.2008.05.017
- Kim JS, Oh D, Yim MJ, Park JJ, Kang KR, Cho IA, Moo SM, Oh JS, You JS, Kim CS, Kim DK, Lee SY, Lee GJ, Im HJ, Kim SG. Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells. Oncol Rep. 2015;33:1775-1782. doi:10.3892/or.2015.3768. https://doi.org/10.3892/or.2015.3768
- Linkds M. Lewis C. Chemoprotectants: a review of their clinical pharmacology and therapeutic efficacy. Drugs. 1999;57:293. https://doi.org/10.2165/00003495-199957030-00003
- Pezzuto JM. Plant-derived anticancer agents. Biochem Pharmacol. 1997;53:121-133. https://doi.org/10.1016/S0006-2952(96)00654-5
- Mlinaric S, Antunovic Dunic J, Skendrovic Babojelic M, Cesar V, Lepedus H. Differential accumulation of photosynthetic proteins regulates diurnal photochemical adjustments of PSII in common fig (Ficus carica L.) leaves. J Plant Physiol. 2017;209:1-10. doi:10.1016/j.jplph.2016.12.002. https://doi.org/10.1016/j.jplph.2016.12.002
- Mawa S, Husain K, Jantan I. Ficus carica L. (Moraceae): phytochemistry, traditional uses and biological activities. Evid Based Complement Alternat Med. 2013;974256. doi:10.1155/2013/974256. https://doi.org/10.1155/2013/974256
- Duke JA, Bugenschutz-godwin MJ, Du collier J, Duke PK. Hand Book of Medicinal Herbs. 2nd ed. Boca Raton: CRC Press; 2002.
- Werbach M. Healing with Food, New York: Harper Collins; 1993.
- Bohlooli S, Mohebipoor A, Mohammadi S, Kouhnavard M, Pashapoor S. Comparative study of fig tree efficacy in the treatment of common warts (Verruca vulgaris) vs. cryotherapy. Int J Dermatol. 2007;46:524-526. https://doi.org/10.1111/j.1365-4632.2007.03159.x
- Lazreg Aref H, Gaaliche B, Fekih A, Mars M, Aouni M, Pierre Chaumon J, Said K. In vitro cytotoxic and antiviral activities of Ficus carica latex extracts. Nat Prod Res. 2011;25:310-319. doi:10.1080/14786419.2010.528758. https://doi.org/10.1080/14786419.2010.528758
- Baeyens-Volant D, Matagne A, El Mahyaoui R, Wattiez R, Azarkan M. A novel form of ficin from Ficus carica latex: Purification and characterization. Phytochemistry. 2015;117:154-167. doi:10.1016/j.phytochem.2015.05.019. https://doi.org/10.1016/j.phytochem.2015.05.019
- Stepek G, Behnke JM, Buttle DJ, Duce IR. Natural plant cysteine proteinases as anthelmintics? Trends Parasitol. 2004;20:322-327. https://doi.org/10.1016/j.pt.2004.05.003
- Baker EN, Drenth J. The cysteine proteinases structure and mechanism. Jurnak F and McPherson A ed. New York: Biological Macromolecules and Assemblies; 1987.
- Solomon A, Golubowicz S, Yablowicz Z, Grossman S, Bergman M, Gottlieb HE, Altman A, Kerem Z, Flaishman MA. Antioxidant activities and anthocyanin content of fresh fruits of common fig (Ficus carica L.). J Agric Food Chem. 2006;54:7717-7723. https://doi.org/10.1021/jf060497h
- Aref HL, Salah KB, Chaumont JP, Fekih A, Aouni M, Said K. In vitro antimicrobial activity of four Ficus carica latex fractions against resistant human pathogens (antimicrobial activity of Ficus carica latex). Pak J Pharm Sci. 2010;23:53-58.
- Wang G, Wang H, Song Y, Jia C, Wang Z, Xu H. Studies on anti-HSV effect of Ficus carica leaves. Zhong Yao Cai. 2004;27:754-756.
- de Amorin A, Borba HR, Carauta JP, Lopes D, Kaplan MA. Anthelmintic activity of the latex of Ficus species. J Ethnopharmacol. 1999;64:255-258. https://doi.org/10.1016/S0378-8741(98)00139-1
- Tezcan G, Tunca B, Bekar A, Yalcin M, Sahin S, Budak F, Cecener G, Eqeli U, Demir C, Guvenc G, Yilmaz G, Erkan LG, Malyer H, Taskapilioqlu MO, Evrensel T, Bilir A. Ficus carica Latex Prevents Invasion Through Induction of Let-7d Expression in GBM Cell Lines. Cell Mol Neurobiol. 2015;35:175-187. doi:10.1007/s10571-014-0109-y. https://doi.org/10.1007/s10571-014-0109-y
- Rubnov S, Kashman Y, Rabinowitz R, Schlesinger M, Mechoulam R. Suppressors of cancer cell proliferation from fig (Ficus carica) resin: isolation and structure elucidation. J Nat Prod. 2001;64:993-996. https://doi.org/10.1021/np000592z
- Raskovic B, Bozovic O, Prodanovic R, Niketic V, Polovic N. Identification, purification and characterization of a novel collagenolytic serine protease from fig (Ficus carica var. Brown Turkey) latex. J Biosci Bioeng. 2014;118:622-627. doi:10.1016/j.jbiosc.2014.05.020. https://doi.org/10.1016/j.jbiosc.2014.05.020
- Hashemi SA, Abediankenari S, Ghasemi M, Azadbakht M, Yousefzadeh Y, Dehpour AA. The Effect of fig Tree Latex (Ficus carica) on Stomach Cancer Line. Iran Red Crescent Med J. 2011;13:272-275.
- Kramer DE, Whitaker JR. Nature of conversion of Ficus carica variety kadota ficin component D to component C. Some physicochemical properties of components C and D. Plant Physiol. 1969;44:1566-1573. https://doi.org/10.1104/pp.44.11.1566
- Zare H, Moosavi-Movahedi AA, Salami M, Mirzaei M, Saboury AA, Sheibani N. Purification and autolysis of the ficin isoforms from fig (Fisucs carica cv. Sabz) latex. Phytochemistry. 2013;87:16-22. doi:10.1016/j.phytochem.2012.12.006. https://doi.org/10.1016/j.phytochem.2012.12.006
- Raskovic B, Lazic J, Polovic N. Characterisation of general proteolytic, milk clotting and antifungal activity of Ficus carica latex during fruit ripening. J Sci Food Agric. 2016;30:576-582. doi:10.1002/jsfa.7126.
- Ullman SB. The inhibitory and necrosis-inducing effects of the latex of Ficus carica L. on transplanted and spontaneous tumours. Exp Med Surg. 1952;10:26-49.
- Khodarahmi GA, Ghasemi N, Hassanzadeh F, Safaie M. Cytotoxic Effects of Different Extracts and Latex of Ficus carica L. on HeLa cell Line. Iran J Pharm Res. 2011;10:273-277.
- Xiang SS, Wang XA, Li HF, Shu YJ, Bao RF, Zhang F, Cao Y, Ye YY, Weng H, Wu WG, Mu JS, Wu XS, Li ML, Hu YP, Jiang L, Tan ZJ, Lu W, Liu F, Liu YB. Schisandrin B induces apoptosis and cell cycle arrest of gallbladder cancer cells. Molecules. 2014;19:13235-13250. doi:10.3390/molecules190913235. https://doi.org/10.3390/molecules190913235
- Ngamkitidechakul C, Jaijoy K, Hansakul P, Soonthornchareonnon N, Sireeratawong S. Antitumour effects of Phyllanthus emblica L.: Induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion of human cancer cells. Phytother Res. 2010;24:1405-1413. doi:10.1002/ptr.3127. https://doi.org/10.1002/ptr.3127