RESUMO
The antiproliferative and cytotoxic activity of glucolaxogenin and its ability to induce apoptosis and autophagy in cervical cancer cells are reported. We ascertained that glucolaxogenin exerts an inhibitory effect on the proliferation of HeLa, CaSki and ViBo cells in a dose-dependent manner. Analysis of DNA distribution in the cell-cycle phase of tumor cells treated with glucolaxogenin suggests that the anti-proliferative activity of this steroid is not always dependent on the cell cycle. Cytotoxic activity was evaluated by detection of the lactate dehydrogenase enzyme in supernatants from tumor cell cultures treated with the steroid. Glucolaxogenin exhibited null cytotoxic activity. With respect to the apoptotic activity, the generation of apoptotic bodies, the presence of active caspase-3 and annexin-V, as well as the DNA fragmentation observed in all tumor lines after treatment with glucolaxogenin suggests that this compound does indeed induce cell death by apoptosis. Also, a significantly increased presence of the LC3-II, LC3 and Lamp-1 proteins was evidenced with the ultrastructural existence of autophagic vacuoles in cells treated with this steroidal glycoside, indicating that glucolaxogenin also induces autophagic cell death. It is important to note that this compound showed no cytotoxic effect and did not affect the proliferative capacity of mononuclear cells obtained from normal human peripheral blood activated by phytohaemagglutinin. Thus, glucolaxogenin is a compound with anti-proliferative properties that induces programmed cell death in cancer cell lines, though it is selective with respect to normal lymphocytic cells. These findings indicate that this glycoside could have a selective action on tumor cells and, therefore, be worthy of consideration as a therapeutic candidate with anti-tumor potential.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Anexina A5/metabolismo , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Feminino , Glicosídeos/metabolismo , Células HeLa , Humanos , L-Lactato Desidrogenase/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Fito-Hemaglutininas/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologiaRESUMO
The scheduled administration of human chorionic gonadotropin in the ovarian stimulation schemes used in Assisted reproduction has made possible to control the ovulatory phenomenon. In order to know the biological repercussion upon the ovule as to elapsed time from HCG and the time of capture, the protocols of Gametes Laboratory, were reviewed; there were 277 cases with this factor. The capture moment was from 32.88 to 41.06 hours from HCG administration, with an average of 36.8 +/- 1.01 hours. There was no significant statistical correlation with the total amount of captured oocytes, useful oocytes, defective oocytes (atresic, broken, degenerated) segmentation rate and embryonary quality. There was a positive, lineal, statistical correlation with the amount of post-mature oocytes (r = 0.35, p = 0.019) and negative with fertilization rate (r = -0.30, p = < 0.0001), both without a correlation among themselves. It was concluded that prolonged time between HCG exposition more than difficulting oocyte capture, negatively affects oocyte quality with a diminution in its possibility of being fertilized. It must be found the optimal window that permits easily obtaining the larger amount of oocytes with the best possibilities of originating healthy pre-embryos.
Assuntos
Gonadotropina Coriônica/administração & dosagem , Fertilização in vitro/métodos , Oócitos/efeitos dos fármacos , Indução da Ovulação/métodos , Gonadotropina Coriônica/farmacocinética , Gonadotropina Coriônica/farmacologia , Feminino , Líquido Folicular , Transferência Intrafalopiana de Gameta , Humanos , Infertilidade Feminina/terapia , Oócitos/fisiologia , Gravidez , Fatores de TempoRESUMO
This study shows that there is certain tendency to asssign more value to the observation of follicular growth by ultrasound than to hormonal levels "per se". However, the appreciation of growth is only part of the phenomenon of development and ovarian maturity, for that, surveillance with hormonal monitor of ovarian response keeps with a most important role in Assisted Reproduction Clinica. The basal levels, mainly of FSH and in a less degree LH, inversely correlate with the amount of retrieved ovocytes. Estradiol values should be interpreted with a fixed point of reference, as the day of HCG administration, and a direct relation is seen between estradiol levels and captured ovocytes; however, is of highest usefulness to value the conduct of estradiol level, with the knowledge that the prognosis for good capture rates improves with ascending values and above 700 pg in the day of HCG administration.
Assuntos
Fase de Clivagem do Zigoto , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Oócitos , Técnicas Reprodutivas , Estatística como AssuntoRESUMO
The increased maternal age was found as responsible for the ovaric biological failure, that in turn, becomes an altered hormonal response, and a reduction in the amount of susceptible ovocytes, susceptible for capture; this diminution in the amount of ovocytes, and not an intrinsic alteration in its quality is at the moment the biological translation of ovarian aging. Therefore, maternal age variable, with its ovarian and endometrial repercussion, becomes the variable with the greatest impact in Assisted Reproduction programs. The variable age is statistically independent from other variables as procedure indication, sterility type, used ovarian stimulation. The patients age should be considered as a very important prognostic factor, when proposing the methods os Assisted Reproduction, independently of the greater risk of gestation problems.
Assuntos
Fase de Clivagem do Zigoto , Fertilização , Idade Materna , Oócitos , Técnicas Reprodutivas , Adulto , Feminino , HumanosRESUMO
The "mouse test" resulted to be an indispensable requisite in order to do, with security, although not complete, the serum selection, to use in the extracorporal phase of FIVTE. Because of the observations it is considered that it should be tried to addition the culture medium with good quality sera; which is evident with a 90% rate, or more, of segmentation in the embryonic system of mouse, of two cells.