Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells.
Curcumin, a component of turmeric, has been reported to exhibit potential antitumor activities. This study assessed the effects of a novel synthetic curcumin analog, EF24, on proliferation, apoptosis, and vascular endothelial growth factor (VEGF) regulation in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells. EF24 time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis. Although treatment with EF24 had no significant effect on VEGF messenger RNA (mRNA) expression,VEGF protein secretion into conditioned media was dose-dependently reduced with EF24 demonstrating ∼8-fold greater potency than curcumin (P < .05). EF24 significantly inhibited hydrogen peroxide (H(2)O(2))-induced VEGF expression, as did the phenolic antioxidant tert-butylhydroquinone (t-BHQ). EF24 upregulated cellular antioxidant responses as observed by the suppression of reactive oxygen species (ROS) generation and activation of antioxidant response element (ARE)-dependent gene transcription. Given its high potency, EF24 is an excellent lead candidate for further development as an adjuvant therapeutic agent in preclinical models of ovarian cancer.
Tan
Xin
X
Department of Vascular Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Sidell
Neil
N
Mancini
Alessandra
A
Huang
Ruo-Pan
RP
Shenming Wang
Horowitz
Ira R
IR
Liotta
Dennis C
DC
Taylor
Robert N
RN
Wieser
Friedrich
F
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000276:immunology*; D001597:Benzylidene Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D010881:Piperidones / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
C524042:3,5-bis(2-fluorobenzylidene)piperidin-4-one; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D010881:Piperidones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D012313:RNA