Prostate cancer is one of the most common malignancies and leading causes of cancer mortality in males. This pathology initially responds to androgen deprivation therapy, but eventually progresses into castration-resistant prostate cancer (CRPC); in this condition the cancer cells acquire the ability to escape cell death and become resistant to current therapies. Cell death is a biological phenomenon that is regulated by multiple cellular processes, including apoptosis and autophagy. Authophagy is a conserved process by which cells recycle macromolecules and organelles, into specialized double-membrane vesicles, known as autophagosomes, that ultimately fuse with lysosomes to generate autophagolysosomes. The role of authophagy in cancer is controversial. In fact, it has been reported that, under stress conditions such as radiation and chemotherapy, autophagy exerts either an antitumoral role by inhibiting cell proliferation or deleterious anti-apoptotic role in tumor cells. In this study we analyzed the effects of the autophagy-inducers trehalose and rapamycin on docetaxel chemoresistance in PC3 cells. The results demonstrated that trehalose was able to reduce the cytotoxic activity of docetaxel, while rapamycin showed a synergic activity on docetaxel–induced cell death. Docetaxel promoted cancer cell apoptosis by inducing mitochondrial loss and damage. When autophagy is activated, damaged mitochondria can be removed by autophagosomes, with a process known as mitophagy. We demostrated that trehalose induces mitophagy and counteracts apoptosis triggered by docetaxel, rapamycin does not cause mitophagy. In conclusion mitophagy is a crucial process in determining the response of cancer cells to anticancer therapy, explaining the phenomenon of chemotherapy-resistance.
Dual role of autophagy on chemoresistance in prostate cancer cells / R. Cristofani, M. Cicardi, M. Montagnani Marelli, M. Marzagalli, F. Fontana, A. Poletti, P. Limonta, R. Moretti. ((Intervento presentato al 17. convegno AIBG tenutosi a Cagliari nel 2016.
|Titolo:||Dual role of autophagy on chemoresistance in prostate cancer cells|
CRISTOFANI, RICCARDO MARIA (Primo)
LIMONTA, PATRIZIA (Penultimo)
MORETTI, ROBERTA MANUELA (Ultimo)
|Data di pubblicazione:||30-set-2016|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
Settore BIO/09 - Fisiologia
|Citazione:||Dual role of autophagy on chemoresistance in prostate cancer cells / R. Cristofani, M. Cicardi, M. Montagnani Marelli, M. Marzagalli, F. Fontana, A. Poletti, P. Limonta, R. Moretti. ((Intervento presentato al 17. convegno AIBG tenutosi a Cagliari nel 2016.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|