Idioma:

Atg5 Regulates Phenethyl Isothiocyanate-Induced Autophagic and Apoptotic Cell Death in Human Prostate Cancer Cells

BOMMAREDDY, Ajay ; HAHM, Eun-Ryeong ; DONG XIAO ; POWOLNY, Anna A ; FISHER, Alfred L ; YU JIANG ; SINGH, Shivendra V

Cancer research (Chicago, Ill.), 2009-04, Vol.69 (8), p.3704-3712 [Periódico revisado por pares]

Philadelphia, PA: American Association for Cancer Research

Texto completo disponível

Citações Citado por

Enviar para

Título:
Atg5 Regulates Phenethyl Isothiocyanate-Induced Autophagic and Apoptotic Cell Death in Human Prostate Cancer Cells
Autor: BOMMAREDDY, Ajay ; HAHM, Eun-Ryeong ; DONG XIAO ; POWOLNY, Anna A ; FISHER, Alfred L ; YU JIANG ; SINGH, Shivendra V
Assuntos: Animals ; Anticarcinogenic Agents - pharmacology ; Antineoplastic agents ; Apoptosis - drug effects ; Autophagy - drug effects ; Autophagy-Related Protein 5 ; Biological and medical sciences ; Caenorhabditis elegans - drug effects ; Cell Line, Tumor ; Gynecology. Andrology. Obstetrics ; Humans ; Isothiocyanates - pharmacology ; Male ; Male genital diseases ; Medical sciences ; Mice ; Mice, Nude ; Microtubule-Associated Proteins - metabolism ; Monomeric GTP-Binding Proteins - biosynthesis ; Nephrology. Urinary tract diseases ; Neuropeptides - biosynthesis ; Oncogene Protein v-akt - metabolism ; Pharmacology. Drug treatments ; Phosphorylation ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Protein Kinases - metabolism ; Ras Homolog Enriched in Brain Protein ; TOR Serine-Threonine Kinases ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland ; Xenograft Model Antitumor Assays
É parte de: Cancer research (Chicago, Ill.), 2009-04, Vol.69 (8), p.3704-3712
Descrição: Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive agent but the mechanism of its anticancer effect is not fully understood. We now show, for the first time, that PEITC treatment triggers Atg5-dependent autophagic and apoptotic cell death in human prostate cancer cells. Exposure of PC-3 (androgen independent, p53 null) and LNCaP (androgen responsive, wild-type p53) human prostate cancer cells to PEITC resulted in several specific features characteristic of autophagy, including appearance of membranous vacuoles, formation of acidic vesicular organelles, and cleavage and recruitment of microtubule-associated protein 1 light chain 3 (LC3) to autophagosomes. A normal human prostate epithelial cell line (PrEC) was markedly more resistant toward PEITC-mediated cleavage and recruitment of LC3 compared with prostate cancer cells. Although PEITC treatment suppressed activating phosphorylations of Akt and mammalian target of rapamycin (mTOR), which are implicated in regulation of autophagy by different stimuli, processing and recruitment of LC3 was only partially/marginally reversed by ectopic expression of constitutively active Akt or overexpression of mTOR-positive regulator Rheb. The PEITC-mediated apoptotic DNA fragmentation was significantly attenuated in the presence of a pharmacologic inhibitor of autophagy (3-methyl adenine). Transient transfection of LNCaP and PC-3 cells with Atg5-specific small interfering RNA conferred significant protection against PEITC-mediated autophagy as well as apoptotic DNA fragmentation. A xenograft model using PC-3 cells and Caenorhabditis elegans expressing a lgg-1:GFP fusion protein provided evidence for occurrence of PEITC-induced autophagy in vivo. In conclusion, the present study indicates that Atg5 plays an important role in regulation of PEITC-induced autophagic and apoptotic cell death.
Editor: Philadelphia, PA: American Association for Cancer Research
Idioma: Inglês

Links

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Atg5 Regulates Phenethyl Isothiocyanate-Induced Autophagic and Apoptotic Cell Death in Human Prostate Cancer Cells

BOMMAREDDY, Ajay ; HAHM, Eun-Ryeong ; DONG XIAO ; POWOLNY, Anna A ; FISHER, Alfred L ; YU JIANG ; SINGH, Shivendra V

Philadelphia, PA: American Association for Cancer Research

Buscando em bases de dados remotas. Favor aguardar.