Isoflavone lupiwighteone induces cytotoxic, apoptotic, and antiangiogenic activities in DU-145 prostate cancer cells.
Isoflavones constitute a large series of compounds found in many plants. They make up an important part of the diet and have a broad spectrum of biological activities such as cytotoxic and antitumor effects. Lupiwighteone (Lup) is an isoflavone-type compound. It is distributed widely in wild-growing plants such as Glycyrrhiza glabra, Lupinus, and Lotus pedunculatus. On the basis of existing research, Lup shows antioxidant and antimicrobial effects, but its antitumor activity has not been reported as yet. This study aimed to examine the antitumor activity of Lup, explore its antitumor mechanism in a human prostate carcinoma cell line (DU-145), and evaluate its antiangiogenetic activity in the human umbilical vein endothelial cell line (HUVEC). The results showed that Lup could inhibit the growth of DU-145 and HUVEC cells in a concentration-dependent and time-dependent manner by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis indicated that Lup could induce cell cycle arrest, cells apoptosis, mitochondrial membrane potential loss, and an increase in intracellular reactive oxygen species of DU-145 cells. Upregulation of Bax, cytochrome c, caspase-3, and PARP-1 protein expressions and downregulation of Bcl-2, procaspase-9, and p-Akt protein expressions were observed by western blot after the treatment of Lup. Furthermore, the effects of Lup on the cellular behavior of HUVECs were also investigated. Altogether, our data proved the anticancer and antiangiogenesis potential of Lup.
Department of Pharmacy, School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou, Jiangsu, People's Republic of China.
Jie
J
Ren
Qianhui
Q
Huang
Yuanyuan
Y
Xu
Meng
M
Yang
Jie
J
Yang
Kun
K
Hu
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011471:Prostatic Neoplasms; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D007529:Isoflavones; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C000602100:lupiwighteone; D019833:Genistein