Back to Search
Start Over
Mycotoxin verrucarin A inhibits proliferation and induces apoptosis in prostate cancer cells by inhibiting prosurvival Akt/NF-kB/mTOR signaling.
- Source :
-
Journal of experimental therapeutics & oncology [J Exp Ther Oncol] 2016 Nov; Vol. 11 (4), pp. 251-260. - Publication Year :
- 2016
-
Abstract
- Trichothecenes are powerful mycotoxins that inhibit protein synthesis and induce ribotoxic stress response in mammalian cells. Verrucarin A (VC-A) is a Type D macrocyclic mycotoxin which inhibits cell proliferation and induces apoptosis in cancer cells. However, the antitumor activity of VC-A for prostate cancer cells has not been investigated. The objective of the present study was to determine the anticancer activity and its mechanism of action in hormone-responsive (LNCaP) and hormone-refractory (PC-3) carcinoma of the prostate (CaP) cell lines. VC-A strongly inhibited the proliferation and induced cell cycle arrest in G2/M phase associated with the inhibition of cell cycle regulatory proteins cyclin D, cyclin E, cyclin-dependent kinases (cdks) cdk2, cdk4, cdk6 and cdk inhibitors WAF1/21 and KIP1/27. VC-A also induced apoptosis in CaP cells as characterized by the cleavage of poly (ADP-ribose) polymerase (PARP-1), procaspases-3, -8 and -9 and the inhibition of Bcl-2 family proteins that regulate apoptosis (Bcl-2, Bcl-xL, Bax, Bak and Bad). In addition, VC-A also down-regulated the expression of prosurvival phospho-AKT (p-AKT), nuclear factor kappa B (NF-kB) (p65) and phospho-mammalian target of rapamycin (p-mTOR) signaling proteins. Taken together, these results demonstrated strong antiproliferative and apoptosis-inducing activity of verrucarin A against CaP cells through cell cycle arrest and inhibition of the prosurvival (antiapoptotic) AKT/NF-kB/mTOR signaling pathway.<br /> (© 2016 Old City Publishing, Inc.)
- Subjects :
- Apoptosis Regulatory Proteins metabolism
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Down-Regulation drug effects
G2 Phase Cell Cycle Checkpoints drug effects
Humans
Male
Mycotoxins pharmacology
Prostate drug effects
Prostate metabolism
Prostatic Neoplasms metabolism
Signal Transduction drug effects
Apoptosis drug effects
Cell Proliferation drug effects
NF-kappa B metabolism
Prostatic Neoplasms drug therapy
Proto-Oncogene Proteins c-akt metabolism
TOR Serine-Threonine Kinases metabolism
Trichothecenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1359-4117
- Volume :
- 11
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of experimental therapeutics & oncology
- Publication Type :
- Academic Journal
- Accession number :
- 27849335