Induction of antiproliferative effect by diosgenin through activation of p53, release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells.
Previously, we demonstrated that a plant steroid, diosgenin, altered cell cycle distribution and induced apoptosis in the human osteosarcoma 1547 cell line. The objective of this study was to investigate if the antiproliferative effect of diosgenin was similar for different human cancer cell lines such as laryngocarcinoma HEp-2 and melanoma M4Beu cells. Moreover, this work essentially focused on the mitochondrial pathway. We found that diosgenin had an important and similar antiproliferative effect on different types of cancer cells. In addition, our new results show that diosgenin-induced apoptosis is caspase-3 dependent with a fall of mitochondrial membrane potential, nuclear localization of AIF and poly (ADP-ribose) polymerase cleavage. Diosgenin treatment also induces p53 activation and cell cycle arrest in the different cell lines studied.
Corbiere
Cecile
C
Laboratoire de Biochimie, UPRES EA 1085, Faculte de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France.
Liagre
Bertrand
B
Terro
Faraj
F
Beneytout
Jean-Louis
JL
D051033:Apoptosis Inducing Factor; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004144:Diosgenin / Q000494:pharmacology*; D005420:Flavoproteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D004144:Diosgenin