Abstract
Some species of the Clusia genus have been shown to have important biomedical properties, including the ability to inhibit tumor growth in vitro and the usefulness for skin care. In this study, we examined the cytotoxic effect of hexane, ethyl acetate and methanol extracts from Clusia latipes Planch. & Triana, Clusiaceae, leaves on survival of human prostate cancer cells (PC-3), colon cancer cells (RKO), astrocytoma cells (D-384), and breast cancer cells (MCF-7). The ethyl acetate extract displayed the most substantial cytotoxic effect. However, using a Comet assay, we observed that the hexane extract induced a genotoxic effect (DNA damage) on human lymphocytes in an in vitro model. Chromatographic purification of the C. latipes hexane extract led to the isolation and identification of friedelin, friedolan-3-ol, and hesperidin as active cytotoxic compounds in hexane extract, while p-amyrine was identified as an active cytotoxic compound in the ethyl acetate extract of C latipes, thereby supporting further studies of the molecular mechanisms underlying the effect of these secondary metabolites on cancer cell survival.
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Aghel, N., Ramezani, Z., Beiranvand, S., 2008. Hesperidin from Citrus sinensis cultivated in Dezful, Iran. Pak. J. Biol. Sci. 11, 2451–2453.
Ahmadi, A., Hosseinimehr, S.J., Naghshvar, F., Hajir, E., Ghahremani, M., 2008. Chemoprotective effects of hesperidin against genotoxicity induced by cyclophosphamide in mice bone marrow cells. Arch. Pharm. Res. 31, 794–797.
Antonisamy, P., Duraipandiyan, V., Ignacimuthu, S., 2011. Anti-inflammatory, analgesic and antipyretic effects of friedelin isolated from Azima tetracantha Lam. in mouse and rat models. J. Pharm. Pharmacol. 63, 1070–1077.
Bailón-Moscoso, N., Romero-Benavides, J.C., Ostrosky-Wegman, P., 2014. Development of anticancer drugs based on the hallmarks of tumor cells. Tumour Biol. 35, 3981–3995.
Balunas, M.J., Kinghorn, A.D., 2005. Drug discovery from medicinal plants. Life Sci. 78, 431–441.
Diaz-Carballo, D., Gustmann, S., Acikelli, A.H., Bardenheuer, W., Buehler, H., Jastrow, H., Ergun, S., Strumberg, D., 2012. 7-Epi-nemorosone from Clusia rosea induces apoptosis, androgen receptor down-regulation and dysregulation of PSA levels in LNCaP prostate carcinoma cells. Phytomedicine 19, 1298–1306.
Ferreira, R.O., de Junior, A.R.C., da Silva, T.M.G., Castro, R.N., da Silva, T.M.S., de Car-valho, M.G., 2014. Distribution of metabolites in galled and non-galled leaves of Clusia lanceolata and its antioxidant activity. Rev. Bras. Farmacogn 24, 617–625.
Gao, X., Wang, W., Wei, S., Li, W., 2009. Review of pharmacological effects of Gly-cyrrhiza radix and its bioactive compounds. Zhongguo Zhong Yao Za Zhi 34, 2695–2700.
Hemshekhar, M., Sunitha, It, Santhosh, M.S., Devaraja, S.S., Kemparaju, It, Vish-wanath, B.S., Niranjana, S.R., Girish, It, 2011. An overview on genus garcinia: phytochemical and therapeutical aspects. Phytochem. Rev 10, 325–351.
Hosseinimehr, S.J., Ahmadi, A., Beiki, D., Habibi, E., Mahmoudzadeh, A., 2009. Protective effects of hesperidin against genotoxicity induced by (99m)Tc-MIBI in human cultured lymphocyte cells. Nucl. Med. Biol 36, 863–867.
Hou, M., Man, M., Man, W., Zhu, W., Hupe, M., Park, It, Crumrine, D., Elias, P.M., Man, M.Q., 2012. Topical hesperidin improves epidermal permeability barrier function and epidermal differentiation in normal murine skin. Exp. Dermatol. 21, 337–340.
Huerta-Reyes, M., Basualdo, M.D.C., Lozada, L., Jimenez-Estrada, M., Soler, C., Reyes-Chilpa, R., 2004. HIV-1 inhibition by extracts of Clusiaceae species from Mexico. Biol. Pharm. Bull 27, 916–920.
Mangas Marin, R., Montes de Oca Porto, R., Bello Alarcón, A., Nival Vázquez, A., 2008. Caracterización por cromatografía de gases/espectrometria de masas del extracto apolar de las hojasde Clusia minor L. Lat. Am. J. Pharm. 27, 747–751.
Monks, N.R., Bordignon, S.A.L., Ferraz, A., Machado, K.R., Faria, D.H., Lopes, R.M., Mondin, C., Souza, I., Lima, M.F.S., da Rocha, A.B., Schwartsmann, G., 2002. Anti-tumour screening of Brazilian plants. Pharm. Biol. 40, 603–616.
Moreira, D.D.L., Teixeira, S.S., Monteiro, M.H.D., De-Oliveira, A.C.A.X., Paumgartten, F.J.R., 2014. Traditional use and safety of herbal medicines. Rev. Bras. Farmacogn. 24, 248–257.
Nagashio, Y., Matsuura, Y., Miyamoto, J., Kometani, T., Suzuki, T., Tanabe, S., 2013. Hesperidin inhibits development of atopic dermatitis-like skin lesions in NC/Nga mice by suppressing Th17 activity. J. Funct. Foods 5, 1633–1641.
Natarajan, N., Thamaraiselvan, R., Lingaiah, H., Srinivasan, P., Maruthaiveeran Periyasamy, B., 2011. Effect of flavonone hesperidin on the apoptosis of human mammary carcinoma cell line MCF-7. Biomed. Prev. Nutr. 1, 207–215.
Park, H.J., Kim, M.J., Ha, E., Chung, J.H., 2008. Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. Phytomedicine 15, 147–151.
Quintans, J.S.S., Costa, E.V., Tavares, J.F., Souza, T.T., Araüjo, S.S., Estevam, C.S., Barison, A., Cabral, A.G.S., Silva, M., Serafini, M., Quintans-Junior, L., 2014. Phytochemical study and antinociceptive effect of the hexanic extract of leaves from Combretum duarteanum and friedelin, a triterpene isolated from the hexanic extract, in orofacial nociceptive protocols. Rev. Bras. Farmacogn. 24, 60–66.
Reyes-Chilpa, R., Estrada-Muniz, E., Apan, T.R., Amekraz, B., Aumelas, A., Jankowski, C.K., Vazquez-Torres, M., 2004. Cytotoxic effects of mammea type coumarins from Calophyllum brasiliense. Life Sci. 75, 1635–1647.
Ribeiro, P.R., Ferraz, C.G., Guedes, M.L.S., Martins, D., Cruz, F.G., 2011. A new biphenyl and antimicrobial activity of extracts and compounds from Clusia burlemarxii. Fitoterapia 82, 1237–1240.
Sahu, B.D., Kuncha, M., Sindhura, G.J., Sistla, R., 2013. Hesperidin attenuates cisplatininduced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine 20, 453–460.
Sordo, M., Herrera, L.A., Ostrosky-Wegman, P., Rojas, E., 2001. Cytotoxic and geno-toxic effects of As, MMA, and DMA on leukocytes and stimulated human lymphocytes. Teratog. Carcinog. Mutagen. 21, 249–260.
Stevens, P., 2007. Clusiaceae-Guttiferae. Flower. Plants Eudicots., pp. 255.
Subhadhirasakul, S., Pechpongs, P., 2005. Aterpenoid and two steroids from the flowers of Mammea siamensis. Songklanakarin J. Sci Technol. 27 (Suppl 2), 555–561.
Suffredini, I.B., Paciencia, M.L., Nepomuceno, D.C., Younes, R.N., Varella, A.D., 2006. Antibacterial and cytotoxic activity of Brazilian plant extracts-Clusiaceae. Mem. Inst. Oswaldo Cruz 101, 287–290.
Tanaka, T., Makita, H., Kawabata, It, Mori, H., Kakumoto, M., Satoh, It, Hara, A., Sumida, T., Ogawa, H., 1997. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin. Carcinogenesis 18, 957–965.
Teixeira, J., Moreira, L., da Guedes, S.M., Cruz, F., 2006. A new biphenyl from Clusia melchioni and a new tocotrienol from C. obdeltifolia. J. Braz. Chem. Soc. 17, 812–815.
Utami, Khalid, R., Sukari, N., Rahmani, M.A., Abdul, M., Dachriyanus, A.B., 2013. Phenolic contents, antioxidant and cytotoxic activities of Elaeocarpus flonbundus Blume. Pak. J. Pharm. Sci. 26, 245–250.
Valadeau, C., Castillo, J.A., Sauvain, M., Lores, A.F., Bourdy, G., 2010. The rainbow hurts my skin: medicinal concepts and plants uses among the Yanesha (Amuesha), an Amazonian Peruvian ethnic group. J. Ethnopharmacol. 127, 175–192.
Acknowledgments
We appreciate the identification of plant material and the technical support provided by Dr. Vladimir Morocho. We thank Dr. Edward Ratovitski (PROMETEO-SENESCYT-Ecuador) for continuous support and invaluable advice during preparation of the manuscript. N.B.M. acknowledges the fellowship awarded by SENESCYT to carry out her Ph.D. studies in the Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México. This article was part of the doctoral thesis of N.B.M.
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NBM (Ph.D. student) contributed by collecting plant samples, conducting the laboratory work, analyzing the data and drafting the paper. MS, JV and LC contributed to the biological studies. JCRB and RS contributed by obtaining extracts and isolating and characterizing secondary metabolites. MMV contributed by critical reading of the manuscript. POW designed the study, supervised the laboratory work and contributed to critical reading of the manuscript. All of the authors read the final manuscript and approved the submission.
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Bailón-Moscoso, N., Romero-Benavides, J.C., Sordo, M. et al. Phytochemical study and evaluation of cytotoxic and genotoxic properties of extracts from Clusia latipes leaves. Rev. Bras. Farmacogn. 26, 44–49 (2016). https://doi.org/10.1016/j.bjp.2015.08.014
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DOI: https://doi.org/10.1016/j.bjp.2015.08.014