Proanthocyanidin Polymer-Rich Fraction of Stryphnodendron adstringens Promotes in Vitro and in Vivo Cancer Cell Death via Oxidative Stress

Cervical cancer is the fourth most common cancer that affects women, mainly through human papilloma virus (HPV) infection with high-risk HPV16 and HPV18. The present study investigated the in vitro anticancer activity and mechanism of action of a proanthocyanidin polymer-rich fraction of Stryphnodendron adstringens (F2) in cervical cancer cell lines, including HeLa (HPV18-positive), SiHa (HPV16-positive), and C33A (HPV-negative) cells, and also evaluated in vivo anticancer activity. In vitro, cell viability was determined by the MTT assay. Cell migration was determined by the wound healing assay. The mechanism of action was investigated by performing ultrastructural analysis and evaluating reactive oxygen species (ROS) production, mitochondrial metabolism, lipoperoxidation, BCL-2 family expression, caspase expression, and DNA and cell membrane integrity. In vivo activity was evaluated using the murine Ehrlich solid tumor model. F2 time- and dose-dependently reduced cell viability and significantly inhibited the migration of cervical cancer cells. HeLa and SiHa cells treated with F2 (IC50) exhibited intense oxidative stress (i.e., increase in ROS and decrease in antioxidant species) and mitochondrial damage (i.e., mitochondrial membrane potential depolarization and a reduction of intracellular levels of adenosine triphosphate). Increases in the Bax/BCL-2 ratio and caspase 9 and caspase 3 expression, were observed, with DNA damage that was sufficient to trigger mitochondria-dependent apoptosis. Cell membrane disruption was observed in C33A cells (IC50 and IC90) and HeLa and SiHa cells (IC90), indicating progress to late apoptosis/necrosis. The inhibition of ROS production by N-acetylcysteine significantly suppressed oxidative stress in all three cell lines. In vivo, F2 significantly reduced tumor volume and weight of the Ehrlich solid tumor, and significantly increased lipoperoxidation, indicating that F2 also induces oxidative stress in the in vivo model. These findings indicate that the proanthocyanidin polymer-rich fraction of S. adstringens may be a potential chemotherapeutic candidate for cancer treatment

Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes

Chemical Study And Antiproliferative, Trypanocidal And Leishmanicidal Activities Of Maxillaria Picta [estudo Químico E Atividades Antiproliferativa, Tripanocida E Leishmanicida De Maxillaria Picta]

The chemical study of the orchid Maxillaria picta resulted in the isolation of the bioactive stilbenes phoyunbene B and phoyunbene C, in addition to four phenolic acids, one xanthone, steroidal compounds and two triterpenes. Crude extract, fractions, subfractions and the isolated xanthone were evaluated for anticancer activity against human tumor cell lines and against evolutionary forms of T. cruzi and L. amazonensis. The structures of the compounds were determined by GC-MS, and 1H NMR, 13C NMR spectral methods as well as bidimensional techniques.37711511157Cechinel Filho, V., (2000) Quim. Nova, 23, p. 680Wang, H., Zhao, T., Che, C.T., (1985) J. Nat. Prod., 48, p. 796Hwang, J.S., Lee, S.A., Hong, S.S., Han, X.H., Lee, C., Kang, S.J., Lee, D., Lee, M.K., (2010) Hwang.Bioorg. Med. Chem. Lett., 20, p. 3785Pomini, A.M., Santin, S.M.O., Silva, C.C., Faria, T.J., Faria, R.T., Ruiz, A.L.T.G., Carvalho, J.E.C., Dela Porte, L.F., (2012) Planta Med., 78, p. 1169Guo, X.Y., Wang, J., Wang, N.L., Kitanaka, S., Liu, H.W., Yao, X.S., (2006) Biol. Pharm. Bull., 54, p. 21Sinha, A.K., Verma, S.C., Sharma, U.K., (2007) J. Sep. Sci., 30, p. 15Gutiérrez, R.P.M., (2010) J. Med. Plants Res., 4, p. 592Estrada, S., López-Guerrero, J.J., Villalobos-Molina, R., Mata, R., (2004) Fitoterapia, 75, p. 690Déciga-Campos, M., Rivero-Cruz, I., Arriaga-Alba, M., Castañeda-Corral, G., Angeles-López, G.E., Navarrete, A., Mata, R., (2007) J. Ethnopharmacol., 110, p. 334Singer, R.B., Koehler, S., (2003) Lankesteriana, 7, p. 57Singer, R.B., (2003) Lankesteriana, 7, p. 111Flach, A., (2005) Tese de Doutorado Universidade Estadual de Campinas, , BrasilMonks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Boyd, M., (1991) J. Natl. Cancer Inst., 83, p. 757Mossmann, T., (1983) J. Immunol. Methods, 65, p. 55Brener, Z., (1962) Rev. Inst. Med. Trop. Sao Paulo, 4, p. 386Ueda-Nakamura, T., Attias, M., Souza, W., (2001) Parasitol. Res., 87, p. 89Brita, E.A., Silva, A.P.B., Ueda-Nakamura, T., Dias-Filho, B.P., Silva, C.C., Sernaglia, R.L., Nakamura, C.V., (2012) PLoS One, 7, p. 12Volpato, H., Desoti, V.C., Cogo, J., Panice, M.R., Sarragiotto, M.H., Silva, S.O., Ueda-Nakamura, T., Nakamura, C.V., (2013) Evid Based Complement Alternat MedOwen, R.W., Haubner, R., Mier, W., Giacosa, A., Hull, W.E., Spiegelhalder, B., Bartsch, H., (2003) Food Chem. Toxicol., 41, p. 703Shirane, N., Murabayashi, A., Masuko, M., Uomori, A., Yoshimura, Y., Seo, S., Uchida, K., Takeda, K., (1990) Phytochemistry, 29, p. 2513Lee, S.Y., Choi, S.U., Lee, J.H., Lee, D.U., Lee, K.R., (2010) Arch. Pharmacal Res., 33, p. 515Goulart, M.O.F., Sant'Ana, A.E.G., Lima, R.A., Calvacante, S., Carvalho, M.G., Braz-Filho, R., (1993) Quim. Nova, 16, p. 95Kim, C.Y., Ahn, M.J., Kim, J., (2007) J. Liq. Chromatogr. Relat. Technol., 29, p. 869Lendl, A., Werner, I., Glasl, S., Kletter, C., Mucaji, P., Presser, A., Reznicek, G., Taylor, D., (2005) Phytochemistry, 66, p. 2381Saito, T., Yamane, H., Murofushi, N., Takahashi, T., Phinney, B.O., (1997) Biosci., Biotechnol., Biochem., 61, p. 1397Ivanova, A., Mikhova, B., Kostova, I., Evstatieva, L., (2010) Chem. Nat. Compd., 46, p. 294Satake, T., (2007) Biol. Pharm. Bull., 30, p. 935Wang, G., Guo, X., Chen, H., Lin, T., Xu, Y., Chen, Q., Liu, J., Yao, X., (2012) Bioorg. Med. Chem. Lett., 22, p. 2114Maruganandan, S., Gupta, S., Kataria, M., Lal, J., Gupta, P.K., (2002) Toxicology, 3, p. 165Maruganandan, S., Gupta, S., Kataria, M., Lal, J., Gupta, P.K., (2005) J. Ethnopharmacol., 97, p. 497Yoshimi, N., Matsunaga, K., Katayama, M., Yamada, Y., Kuno, T., Qiao, Z., Hara, A., Mori, H., (2001) Cancer Lett., 163, p. 163Wang, R.R., Gao, Y.D., Ma, C.H., Zhang, X.J., Huang, C.G., Huang, J.F., Zheng, Y.T., (2011) Molecules, 16, p. 4264Chen, Y.H., Chang, F.R., Lin, Y.J., Hsieh, P.W., Wub, M.J., Wu, Y.C., (2008) Food Chem., 2, p. 684García, D., Escalante, M., Delgado, R., Ubeira, F.M., Leiro, J., (2003) Phytother. Res., 17, p. 1203Jagetia, G.C., Baliga, M.S., (2005) Phytomedicine, 12, p. 209Leiro, J., Arranz, J.A., Yáñes, M., Ubeira, F.M., Sanmartín, M.L., Orallo, F., (2004) Int. J. Immunopharmacol., 4, p. 76

Fluorescence properties of curcumin-loaded nanoparticles for cell tracking

Bassam Felipe Mogharbel,1 Julio Cesar Francisco,1 Ana Carolina Irioda,1 Dilcele Silva Moreira Dziedzic,1 Priscila Elias Ferreira,1 Daiany de Souza,1 Carolina Maria Costa de Oliveira Souza,1 Nelson Bergonse Neto,2 Luiz Cesar Guarita-Souza,2 Celia Regina Cavichiolo Franco,3 Celso Vataru Nakamura,4 Vanessa Kaplum,4 Letícia Mazzarino,5 Elenara Lemos-Senna,6 Redouane Borsali,7 Paula A Soto,8 Patricia Setton-Avruj,8 Eltyeb Abdelwahid,9 Katherine Athayde Teixeira de Carvalho1 1Cell Therapy and Biotechnology in Regenerative Medicine Department, Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research and Pequeno Príncipe Faculty, Curitiba, Paraná, Brazil; 2Institute of Biological and Health Sciences, Pontifical Catholic University of Paraná (PUCPR), Centro de Ciências Biológicas e da Saúde (CCBS), Curitiba, Brazil; 3Cell Biology Department, Federal University of Paraná, Curitiba, Paraná, Brazil; 4Department of Pharmaceutical Sciences, Universidade Estadual de Maringá, Maringá, Paraná, Brazil; 5Department of Pharmaceutical Sciences, NanoBioMat Laboratory, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil; 6Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil; 7Centre de Recherches sur les Macromolécules Végétales (CERMAV), Centre National de la Recherche Scientifique (CNRS), University Grenoble Alpes, F-38000, Grenoble, France; 8Instituto de Química y Físicoquímica Biológica (IQUIFIB), Departament of Química Biológica, Facultad de Farmacia y Bíoquímica, Universidad de Buenos Aires (UBA) Consejo nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentine; 9Feinberg School of Medicine, Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, Il, USA Background: Posttransplant cell tracking, via stem cell labeling, is a crucial strategy for monitoring and maximizing benefits of cell-based therapies. The structures and functionalities of polysaccharides, proteins, and lipids allow their utilization in nanotechnology systems. Materials and methods: In the present study, we analyzed the potential benefit of curcumin-loaded nanoparticles (NPC) using Vero cells (in vitro) and NPC-labeled adipose-derived mesenchymal stem cells (NPC-ADMSCs) (in vivo) in myocardial infarction and sciatic nerve crush preclinical models. Thereafter, transplantation, histological examination, real time imaging, and assessment of tissue regeneration were done. Results: Transplanted NPC-ADMSCs were clearly identified and revealed potential benefit when used in cell tracking. Conclusion: This approach may have broad applications in modeling labeled transplanted cells and in developing improved stem cell therapeutic strategies. Keywords: mesenchymal stem cells, transplantation, cell marking, myocardium infarction, sciatic nerve crus

CHEMICAL STUDY AND ANTIPROLIFERATIVE, TRYPANOCIDAL AND LEISHMANICIDAL ACTIVITIES OF Maxillaria picta

The chemical study of the orchid Maxillaria picta resulted in the isolation of the bioactive stilbenes phoyunbene B and phoyunbene C, in addition to four phenolic acids, one xanthone, steroidal compounds and two triterpenes. Crude extract, fractions, subfractions and the isolated xanthone were evaluated for anticancer activity against human tumor cell lines and against evolutionary forms of T. cruzi and L. amazonensis. The structures of the compounds were determined by GC-MS, and ¹H NMR, 13C NMR spectral methods as well as bidimensional techniques