title: [Rapamycin effect on senescence and autophagy processes in human cell lines].
abstract: Autophagy and senescence are both processes that firstly avoid tumor development through the inhibition of proliferation of damaged cells. However, autophagy does not imply cell death, because it is also a mechanism of cell survival under stress conditions. Concerning senescence, although these cells do not proliferate, they produce growth factors that contribute to the proliferative response of other cells. Rapamycin is an immunosupressor used in transplanted patients that inhibits the mTOR transduction signal pathway. This pathway is involved in the control of the energetic and nutritional state of the cell allowing protein synthesis and inhibiting autophagy when it is active. In this paper, the action of rapamycin over these processes was investigated and we found that a low concentration of this drug induces the senescence of a normal cell line, while a higher concentration induces autophagy of a transformed cell line. We have also determined that the oncogen RAC3 inhibits autophagy and that its expression is diminished by rapamycin. Therefore, our results contribute to a better understanding of the molecular mechanisms by which this drug is effective, given the relevance of rapamycin for potential tumor therapy.
authors: Laboratorio de Biología Molecular y Apoptosis, Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, IDIM-CONICET, Buenos Aires, Argentina.
authors: Pablo N
authors: PN
authors: Fernández Larrosa
authors: Marina
authors: M
authors: Ruiz Grecco
authors: Cecilia V
authors: CV
authors: Alvarado
authors: Sabrina
authors: S
authors: Micenmacher
authors: Cristina
authors: C
authors: Aguirre
authors: Giselle
authors: G
authors: Martínez Noel
authors: Mónica A
authors: MA
authors: Costas
authors: María Fernanda
authors: MF
authors: Rubio
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000502:physiology; D016922:Cellular Senescence / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008954:Models, Biological; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus