Antiproliferative Activity And Induction Of Apoptosis In Pc-3 Cells By The Chalcone Cardamonin From Campomanesia Adamantium (myrtaceae) In A Bioactivity-guided Study

The Myrtaceae family is a common source of medicines used in the treatment of numerous diseases in South America. In Brazil, fruits of the Campomanesia species are widely used to make liqueurs, juices and sweets, whereas leaves are traditionally employedas a medicine for dysentery, stomach problems, diarrhea, cystitis and urethritis. Ethanol extracts of Campomanesia adamantium (Myrtaceae) leaves and fruits were evaluated against prostate cancer cells (PC-3). The compound (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3- phenylprop-2-en-1-one, cardamonin) was isolated from ethanol extracts of C. adamantium leaves in a bioactivity-guided study and quantified by UPLC-MS/MS. In vitro studies showed that the isolated chalcone cardamonin inhibited prostate cancer cell proliferation and decreased the expression of NFkB1. Moreover, analysis by flow cytometry showed that this compound induced DNA fragmentation, suggesting an effect on apoptosis induction in the PC-3 cell line. © 2014 by the authors; licensee MDPI, Basel, Switzerland.19218431855Brandão, H.N., David, J.P., Couto, R.D., Nascimento, J.A.P., David, J.M., Química e farmacologia de quimioterápicos antineoplásicos derivados de plantas (2010) Quim. Nova, 33, pp. 1359-1369Newman, D.J., Cragg, G.M., Snader, K.M., Natural products as sources of new drugs over the period 1981-2002 (2003) J. Nat. Prod., 66, pp. 1022-1037Newman, D.J., Cragg, G.M., Snader, K.M., Natural products as sources of new drugs over the 30 years from 1981 to 2010 (2012) J. Nat. Prod., 75, pp. 311-335Stefanello, M.E.A., Pascoal, A.C.R.F., Salvador, M.J., Essential oils from neo-tropical myrtaceae: Chemical diversity and biological properties (2011) Chem. Biodivers., 8, pp. 73-94Lorenzi, H., Árvores brasileiras: Manual de identificação e cultivo de plantas arböreas nativas do brasil, 1st ed (2002) Editora Plantarum: Nova Odessa, p. 352. , BrazilPavan, F.R., Leite, C.Q.F., Coelho, R.G., Coutinho, I.D., Honda, N.K., Cardoso, C.A.L., Vilegas, W., Sato, D.N., Evaluation of anti-mycobacterium tuberculosis activity of campomanesia adamantium (myrtaceae (2009) Quim. Nova, 32, pp. 1222-1226Coutinho, I.D., Coelho, R.G., Kataoka, V.M.F., Honda, N.K., Silva, J.R.M., Vilegas, W., Cardoso, C.A.L., Determination of phenolic compounds and evaluation of antioxidant capacity of campomanesia adamantium leaves (2008) Ecletíca Quím., 33, pp. 53-60Pascoal, A.C.R.F., Erenfried, C.A., Eberlin, M.N., Stefanello, M.E.A., Salvador, M.J., Free radical scavenging activity, determination of phenolic compounds and hplc-dad/esi-ms profile of campomanesia adamantium leaves (2011) Nat. Prod. Commun., (6), pp. 969-972Ferreira, L.C., Grabe-Guimarães, A., De Paula, C.A., Michel, M.C.P., Guimarães, R.G., Rezende, S.A., De Souza-Filho, J.D., Guimarães, D.A.S., Anti-inflammatory and antinociceptive activities of campomanesia adamantium (2013) J. Ethnopharmacol., 145, pp. 100-108Zi, X., Simoneau, A.R., Flavokawain, A., A novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice (2005) Cancer Res., 65, pp. 3479-3486Solomon, V.R., Lee, H., Anti-breast cancer activity of heteroaryl chalcone derivatives (2012) Biomed. Pharmacother., 66, pp. 213-220Itokawa, H., Morita, M., Mihashi, S., Phenolic compounds from the rhizomes of alpinia speciosa (1981) Phytochemistry, 20, pp. 2503-2506Kamal, A., Mallareddy, A., Suresh, P., Shaik, T.B., Lakshma-Nayak, V., Kishor, C., Shetti, R.V., Ramakrishna, S., Synthesis of chalcone-amidobenzothiazole conjugates as antimitotic and apoptotic inducing agents (2012) Bioorg. Med. Chem., 20, pp. 3480-3492Baldwin, A.S., Series introduction: The transcription factor of nfk-b and humam disease (2001) J. Clin. Invest., 107, pp. 3-6Karin, M., Cao, Y., Greten, F.R., Li, Z.W., Nfk-b in cancer: From innocent bystander to major culprit (2002) Nat. Rev. Cancer, 2, pp. 301-310Luo, J.L., Maeda, S., Hsu, L.C., Yagita, H., Karin, M., Inhibition of nfk-b in cancer cells converts inflammation-induced tumor growth mediated by tnfa to trail-mediated tumor regression (2004) Cancer Cell., 6, pp. 297-305Sladkova, L.V., Moskaleva, E.V., Posypanova, G.A., Apoptosis of cells of different lines and the characteristics of internucleosomal dna fragmentation in cells: Connection with the cell cycle (2000) Tsitologiia, 42, pp. 309-313Rahman, M.A., Chalcone: A valuable insight into the recent advances and potential pharmacological activities (2011) Chem. Sci. J., 29, pp. 1-16Syam, S., Abdelwahab, S.I., Al-Mamary, M.A., Mohan, S., Synthesis of chalcones with anticancer activities (2012) Molecules, 17, pp. 6179-6195Szliszka, E., Czuba, Z.P., Mazur, B., Paradysz, A., Krol, W., Chalcones and dihydrochalcones augment trail-mediated apoptosis in prostate cancer cells (2010) Molecules, 15, pp. 5336-5353Simirgiotis, M.J., Adachi, S., To, S., Yanga, H., Reynertson, K.A., Basile, M., Gil, J.R.R., Kennellya, E.J., Cytotoxic chalcones and antioxidants from the fruits of syzygium samarangense wax jambu (2008) Food Chem., 107, pp. 813-819Park, S., Gwak, J., Han, S.J., Oh, S., Cardamonin suppresses the proliferation of colon cancer cells by promoting β-catenin degradation (2013) Biolog. Pharm. Bull., 36, pp. 1040-1044Qin, Y., Sun, C.Y., Lu, F.R., Shu, X.R., Yang, D., Chen, L., She, X.M., Hu, Y., Cardamonin exerts potent activity against multiple myeloma through blockade of nf-κb pathway in vitro Leuk. Res., 2012 (36), pp. 514-520Teodori, E., Dei, S., Scapecchi, S., Gualtieri, F., The medicinal chemistry of multidrug resistence reversing drugs (mrd (2002) Farmaco, 57, pp. 385-414Baguley, B.C., Multiple drug resistence mechanisms in cancer (2010) Mol. Biotechnol., 46, pp. 308-316Kale, A., Gawande, S., Kotwal, S., Cancer phytotherapeutics: Role for flavonoids at the cellular level (2008) Phytother. Res., 22, pp. 567-577Skehan, P., Storeng, R., Scudiero, D., Monks, A., Mcmahon, J., Vistica, D., Warren, J.T., Boyd, M.R., New colorimetric cytotoxicity assay for anticancer-drug screening (1990) J. Nat. Cancer Instit., 82, pp. 1107-1118Shoemaker, R.H., The nci60 human tumour cell line anticancer drug screen (2006) Nat. Rev. Cancer, 6, pp. 813-823Nicoletti-Carvalho, J.E., Nogueira, T.C.A., Gorjão, R., Bromati, C.R., Yamanaka, T.S., Boschero, A.C., Velloso, L.A., Bordin, S., Upr-mediated trib3 expression correlates with reduced akt phosphorylation and inability of interleukin 6 to overcome palmitate-induced apoptosis in rinm5f cells (2010) J. Endocrinol., 206, pp. 183-19