ABSTRACT
El cáncer de mama (CM) es el tumor más frecuente entre las mujeres. Aproximadamente, el 75% de los casos son receptor de estrógeno (ER) positivo. En particular, ERα promueve el desarrollo tumoral mientras que ERβ tendría efectos anti-proliferativos. Ha sido demostrado que los acidos grasos poliinsaturados (PUFAs) y sus derivados modulan el proceso carcinogénico. Sin embargo, aún no se conocen totalmente los mecanismos que emplean estas moléculas para regular este proceso. Nos propusimos estudiar el efecto de los PUFAs ω-3 en variables biológicas implicadas en el desarrollo de un carcinoma de mama murino, tanto in vivo como in vitro. El aceite de chía es rico en ácido αlinolénico (ALA 18:3 ω-3), mientras que el de maíz es fuente de ácido linoleico (LA 18:2 ω-6). ALA y LA son precursores de eicosanoides con efectos opuestos en el CM y también producen especies reactivas del oxígeno (ROS) que pueden modular la expresión de NFκB, un factor de transcripción con un rol controversial en la carcinogénesis. Nos propusimos determinar los posibles procesos que pueden ser activados por los PUFAs ω-3 en el CM. 40 ratones BALB/c fueron alimentados con una dieta rica en aceite de chía (ChO) o aceite de maíz (CO) y se inocularon con una línea celular murina de CM, LM3. Después de 35 días, la incidencia tumoral fue mayor en los ratones alimentados con CO en comparación con los ratones alimentados con ChO (100 vs 85%, p <0,05). El peso (1,0±0,2 vs 2,2±0,2 g, p <0,05) y el volumen tumoral (4,4±0,4 vs 7,2 ± 1,0 mm3, p <0,05), así como el número de metástasis (7,4±0,8 vs 10,0±0,1, p <0.05) fueron más bajos, mientras que el tiempo de latencia del tumor (22±1 vs 15±2 d, p <0,05) fue mayor en los ratones alimentados con la dieta ChO. Se observó una disminución del número de mitosis y un mayor número de cuerpos apoptóticos, además de una mayor infiltración de linfocitos-T (células CD3+) en el grupo ChO, respecto del grupo CO (p <0,05).
Breast cancer (BC) is the most common tumour where estrogen receptor (ER) plays a key role. ERα promotes tumour growth, while ERβ has an anti-proliferative effect. It has been demonstrated that ω-3 polyunsaturated fatty acid (PUFA) consumption as well as its derivated metabolites are allowed to modulate carcinogenesis although the molecular mechanisms are not fully understood. The study was aimed to determine the possible mechanisms that are activated by dietary lipids regulating BC growth in-vivo and in-vitro. Chia oil is rich in α-linolenic acid (ALA 18:3 ω-3), while corn oil is rich in linoleic acid (LA 18:2 ω-6). ALA and LA are precursors of eicosanoid with opposite effects in BC and also generate reactive oxygen species (ROS), which could affect NFκB, a transcription factor with a controversial role in carcinogenesis. 40 BALB/c mice were fed with a diet rich in Chia Oil (ChO) or Corn Oil (CO) and inoculated with LM3, a BC murine cell line. After 35 days, tumour incidence was higher in CO-fed mice compared with ChO-fed mice (100 vs 85%, p <0.05). Tumour weight (1.0±0.2 vs 2.2±0.2 g, p <0.05) and volume (4.4±0.4 vs 7.2±1.0 mm, p <0.05) as well as metastasis number (7.4±0.8 vs 10.0±0.1, p <0.05) were lower, whereas tumour latency time (22±1 vs 15±2 d, p <0.05) was longer in ChO-fed mice. A lower number of mitosis and a higher number of apoptotic bodies besides higher T-lymphocyte infiltration was observed in ChO with respect to COgroup (p <0.05). Tumours cell membranes from ChO-fed mice showed a higher percentage of PUFAs ω-3 compared with those from CO-fed mice and generated lower amounts of ω-6 pro-inflammatory eicosanoids such as 13(S)-HODE, 15(S)HETE and 5(S)-HETE (p <0.05).
Subject(s)
Male , Female , Humans , Breast Neoplasms , Fatty Acids/immunology , /immunology , Estrogen Receptor beta , NF-kappa B , ArgentinaABSTRACT
Molecular cloning of components of protective antigenic preparations have suggested that related parasite fatty acid binding proteins could form the basis of the well documented protective, immune cross reactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. We have now confirmed the cross protective potential of parasite fatty acid binding proteins and suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni of veterinary and human importance respectively.
Subject(s)
Humans , Animals , Mice , Rabbits , Antigens, Helminth/immunology , Fasciola hepatica , Fascioliasis/prevention & control , Schistosoma mansoni , Schistosomiasis mansoni , Vaccination , Vaccines, Synthetic/immunology , Fatty Acids/immunology , /immunology , Carrier Proteins/immunologyABSTRACT
Vaccines in schistosomiasis using homologous antigens have been studied extensively in experimentally infected mammalian hosts. Vaccines using heterologous antigens have received comparatively less attention. This review summarizes recent work on a heterologous 12 kDa Fasciola hepatica antigenic polypeptide which cross reacts with Schistosoma mansoni. A cDNA has been cloned and sequenced, and the predicted amino acid sequence of the recombinant protein has been shown to have significant (44) identity with a 14 kDa S. mansoni fatty acid binding protein. Thus in the parasitic trematodes fatty acid binding proteins may be potential vaccine candidates. The F. hepatica recombinant protein has been overexpressed and purified and denoted rFh15. Preliminary rFh15 migrates more slowly (i.e. may be slightly larger) than nFh12 on SDS-PAGE and has a predicted pI of 6.01 vs. observed pI of 5.45. Mice infected with F. hepatica develop antibodies to nFh12 by 2 weeks of infection vs. 6 weeks of infection to rFh15; on the other hand, mice with schistosomiasis mansoni develop antibodies to both nFh12 and rFh15 by 6 weeks of infection. Both the F. hepatica and S. mansoni cross-reactive antigens may be cross-protective antigens with the protection inducing capability against both species.