Ascorbyl stearate inhibits cell proliferation and tumor growth in human ovarian carcinoma cells by targeting the PI3K/AKT pathway.
Ascorbyl stearate is a lipophilic, vitamin C derivative with antitumorigenic properties. The molecular mechanism(s) underlying the anticarcinogenic effect of this compound have not been well documented. The effect of ascorbyl stearate was studied in a panel of human ovarian epithelial cancer cells. Treatment with ascorbyl stearate caused a dose-dependent inhibition of the cell proliferation. The antiproliferative effect was due to the arrest of cells in the S/G2-M-phase of the cell cycle. Treatment of OVCAR-3 cells with ascorbyl stearate also inhibited PI3K/AKT activity. The presence of a constitutively active AKT protected OVCAR-3 cells from the effects of ascorbyl stearate, suggesting that this nutraceutical targets the PI3K/AKT pathway. The administration of ascorbyl stearate by gavage induced involution of human ovarian carcinoma xenografts in nude mice. These studies indicate that the antiproliferative effect of ascorbyl stearate on ovarian epithelial cancer cells is associated with decreased PI3K/AKT activity, and point toward the PI3K/AKT signaling pathway as a target for this drug.
Department of Pathology Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, College of Medicine, Tampa, FL 33612, USA.
Quan
Q
Fang
K Akhilender
KA
Naidu
Kamatham A
KA
Naidu
Haiyan
H
Zhao
Mei
M
Sun
Han C
HC
Dan
Aejaz
A
Nasir
Hans E
HE
Kaiser
Jin Q
JQ
Cheng
Santo V
SV
Nicosia
Domenico
D
Coppola
D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001205:Ascorbic Acid; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C036225:ascorbyl monostearate