In Vitro and in Vivo Antineoplastic Activity of Barbatic Acid
Keywords:Antitumor, Citotoxity activity, Depside, Lichen, Lichen substance, Natural Compound
Background: Lichen compounds exhibit remarkable biological activity. Several of them are potent anticancer agent and some with low or none toxicity. The aim of this study was perform in vitro and in vivo assessments of the antineoplastic activity of organic extract and barbatic acid (BAR) isolated from the lichen Cladia aggregata (Sw.) Nyl.
Â Methods: In vitro assays were performed with both extract and BAR against HEp-2 (Adenocarcinoma of the Larynx), NCI-H292 (Squamous Cell Lung Carcinoma) and KB (Nasopharyngeal Squamous Cell Carcinoma) cells. The tests were carried out on the Sarcoma-180 BAR, tumor and organs were analyzed histopatologically after 7 days of chemotherapy.
Â Results: Cytotoxic tests with BAR revealed 50% inhibitory concentration (IC50) of 19.06 Âµg mL-1 for NCI-H292 and 12.0 Âµg mL-1 for KB and 6.25 Âµg mL-1 for HEp-2 cells. Tests with Sarcoma-180 demonstrated 46.3% inhibitory activity against the tumor by BAR. This substance showed no significant effect on the expression of argyrophilic nucleolar organizer regions proteins (AgNORs). The histopathology study of neoplastic tissue, demonstrated that cell proliferation was not affected by the antineoplastic action of the compound tested.
Â Conclusions: The results indicate that barbatic acid exhibits significant antineoplastic activity and low toxicity rate.
BaÄkorovÃ¡ M, BaÄkor M, MikeÅ¡ J, JendÅ¾elovskÃ½ R, FedoroÄko P. Variable responses of different human cancer cells to the lichen compounds parietin, atranorin, usnic acid and gyrophoric acid. Toxicol in Vitro 2011, 25: 37-44.
Hawksworth DL, Honegger R. The lichen thallus: a symbiotic phenotype of nutritionally specialized fungi and its response to gal produces. Claredon Press. pp. 77-98. 1994.
Shrestha G, El-Naggar AM, St Clair LL, Oâ€™Neill K. Anticancer Activities of Selected Species of North American Lichen Extracts. Phytother. Res 2015, 29: 100â€“107.
Morita H, Tsuchiya T, Kishibe K, Noya S, Shiro M, Hirasawa Y. 2009. Antimitotic activity of labaric acid and a new benzofuran, sakisacaulon a from Stereocaulon sasakii. Bioorg Med Chem Lett 2009, 19: 3679-3681.
KosaniÄ‡ M, RankoviÄ‡ B, StanojkoviÄ‡ T, RanciÄ‡ A, ManojloviÄ‡ N. Cladonia lichens and their major metabolites as possible natural antioxidant, antimicrobial and anticancer agentes. LWT - Food Sci Technol 2014, 59: 518-525.
Martins MCB, Lima MJG, Silva FP, Azevedo-Ximenes E, Silva NH, Pereira EC. Cladia aggregata (lichen) from Brazilian Northeast: chemical characterization and antimicrobial activity. Braz Arch Biol Technol 2010, 53: 115-122.
NÃ³brega NA, Ribeiro SM, Pereira EC, Marcelli M, Martins MCB, FalcÃ£o EPS, GusmÃ£o NB, Silva NH. 2012. ProduÃ§Ã£o de compostos fenÃ³licos a partir de cÃ©lulas imobilizadas do lÃquen Parmotrema andinum (MÃ¼ll. Arg.) Hale e avaliaÃ§Ã£o de atividade antimicrobiana. Acta Bot Bras 2012, 26: 101-107.
Ari F, Celikler S, Oran S, Balikci N, Ozturk S, Ozel MZ, Ozyurt D, Ulukaya E. Genotoxic, cytotoxic, and apoptptic effects of Hypogymnia physodes (L.) Nyl. on breast cancer cells. Environ Toxicol 2012. DOI 10.1002/tox.
KosaniÄ‡ M, RankoviÄ‡ B, StanojkoviÄ‡ T. Investigation of selected serbian lichens antioxidant, antimicrobial and anticancer properties. J Anim Plant Sci 2013, 23: 1628-1633.
Lima RMC, Nascimento SC, Pereira EC, Campos-Takaki GM. Atividade citotÃ³xica e antitumoral de extratos liquÃªnicos. Bol Soc Brot., 1990, v. 63, p. 339-348.
Santos NPS, Nascimento SC, Wanderley MSO, Pontes-Filho NT, Castro CMMB, Pereira EC, Silva NH, Honda NK, MagalhÃ£es NSS. Nanoencapsulation of Usnic Acid: An Attempt to Improve Antitumour Activity end Reduce Hepatotoxicity. Eur J Pharm Biopharm 2006, 64: 154-160.
Moo- Sung K, Hong-Bum C. Melanogenesis inhibitory effects of methanolic extracts of Umbilicaria esculenta and Usnea longissima. J Microbiol 2007, 45: 578-582.
Russo A, Piovano M, Lombardo L, Garbarino J, Cardile V. Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sci 2008, 83: 468-474.
Oâ€™Neill MA, Mayer M, Murray KE, Rolim-Santos HML, Santos-MagalhÃ£es NS, Thompson AM, Appleyard VCL. Does usnic acid affect microtubules in human cancer cells? Brazilian Journal Biol 2010, 70: 659-664.
Carvalho TUM, Attias M, Cunha e Silva NL, Carvalho TU. MÃ©todos de estudo da cÃ©lula. Cultura de cÃ©lulas animais. EditoraÃ§Ã£o eletrÃ´nica-Fenorte/VENT, Rio de Janeiro, Brasil. 1996.
Geran RH, Greenberg GNH. 1990. Protocol for screening of agent and natural products against animal tumors and other biological system. Cancer Chemoth Rep 1990, 3: 1-103.
Karber G, Behrens B. Statistical methods in biological assay. Ed. Griffin Ch. and C. London. England. 1964.
Berlion M. Mise au point dâ€™un system de selection de substances antitumorales: application a lâ€™etude dâ€™analogues struturaux de la geopetaline (Doctorâ€™s thesis). Grenoble: Universite Joseph Berlion; 1988.
Ploton D, Menager M, Jeannesson P, Himber G, Pigeon F, Adnett JJ. Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer region at the optical level. Histoche J 1986 l18: 5-14.
Burlando B, Ranzato E, Volente A, Appendino G, Pollastro F, Verotta L. Antiproliferative effects on tumour cells and promotion of keratinocyte wound healing by different lichen compounds. Planta Med 2009, 75: 607-613.
EinarsdÃ³ttir E, Groeneweg J, BjÃ¶rnsdÃ³ttir GG, HarÃ°ardottir G, OmarsdÃ³ttir S, IngÃ³lfsdÃ³ttir K, Ã–gmundsdÃ³ttit HM. Cellular mechanisms of the anticancer effects of the lichen compound usnic acid. Planta Med 2010, 76: 969-974.
FernÃ¡ndez-Morino C, Divakar PK, Crespo A, GÃ³mez-Serranillos MP. Neuroprotective activity and cytotoxic potential of two Parmeliaceae lichens: identification of active compounds. Phytomedicine 2015. DOI 10.1016/j.phymed.2015.06.005.
Pereira EC, Nascimento SC, Lima RMC, Silva NH, Oliveira AFM, Boitard M, Vicente C, Legaz ME. 1994. Analysis of Usnea fasciata crude extracts with antineoplasic activity. Tokai J Exp Clin Med 1994, 19: 47-52.
Torres-Montaner A, Huq M. Histopathological study comparing upstream binding factor expression and AgNOR staining. Cell Prolif 2012, 45: 45-51.
TrerÃ¨ D. AgNOR staining and quantification. Micron. 2000, v. 31, p. 127-31.
Mondal NK, Ghosh S, Ray MR. Quantitative analysis of AgNOR proteins in buccal epithelial cells of Indian street boys addicted to gasp 'golden glue'. Exp Toxicol Pathol 2011, 63: 677-81.
Tomobe M, Shimazui T, Uchida K, Akaza H. AgNOR count in resting cells (resting NOR) is a new prognostic marker in invasive bladder tumor. Anal Cell Pathol 2001, 22: 193-199.
BaÄkorova M, JendÅ¾elovskÃ½ R, Kello M, BaÄkor M, MikeÅ¡ J, FedoroÄko P. Lichen secondary metabolites are responsible for induction of apoptosis in HT-29 and A2780 human cancer cell lines. Toxicol in Vitro 2012, 26: 468.
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