Journal
CELL DEATH & DISEASE
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2016.134
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Funding
- Pontificia Universidad Javeriana, via the project entitled 'Evaluacion de la actividad antitumoral de una fraccion de Caesalpinia spinosa, en un modelo murino de melanoma' [120110X0401200]
- COLCIENCIAS through the project entitled, 'Estudio de la respuesta inmune generada luego de la terapia antitumoral con P2Et y Galactomanano en un modelo murino de melanoma metastasico', Bogota, Colombia [120113I0101103]
- Swiss National Science Foundation [31003A_156469]
- [120813I0401200]
- Swiss National Science Foundation (SNF) [31003A_156469] Funding Source: Swiss National Science Foundation (SNF)
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Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-gamma) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et's anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et's anti-tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells.
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