title: Deltonin, a steroidal saponin, inhibits colon cancer cell growth in vitro and tumor growth in vivo via induction of apoptosis and antiangiogenesis.
abstract: Deltonin, a steroidal saponin, isolated from Dioscorea zingiberensis Wright (DZW), has shown high-cytotoxic activity in cancer cells. However, its mechanisms and in vivo anti-cancer effects remain unknown. In the present study, we evaluated the effects and explored the anti-tumor mechanisms of deltonin on a panel of colon cancer cell lines and in a mouse model of murine colon cancer C26. Deltonin had more cytotoxic effect on C26 cells than 5-fluorouracil had, promoting dramatic G2-M phase arrest and apoptosis in C26 cells in a concentration-dependent manner; oral administration of deltonin significantly inhibited the tumor growth and prolonged survival of the tumor bearing mice. The deltonin treatment caused a noticeable apoptosis in tumor tissue, which associated with increased levels of Bax, activated caspase-3, caspase-9, and cleaved poly (ADPribose) polymerase, decreased pro-caspase-8, pro-caspase-9, Bcl-2 expression levels and extracellular signal-regulated kinase-1/2 activity; and dose-dependently inhibit angiogenesis. In conclusion, the findings in this study demonstrated that deltonin is an effective natural agent for cancer therapy, which may be mediated, in part, by induction of apoptosis, as well as involve mitogen-activated protein kinase pathways, and inhibition of angiogenesis.
authors.affiliation: Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, and State Key Laboratory of Biotherapy, West China Hospital, Chengdu, China.
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Tong
authors.forename: Yong
authors.initials: Y
authors.lastname: Qing
authors.forename: Dan
authors.initials: D
authors.lastname: Shu
authors.forename: Yang
authors.initials: Y
authors.lastname: He
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Zhen-Ling
authors.initials: ZL
authors.lastname: Wang
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Zhang
authors.forename: Zhi-hua
authors.initials: ZH
authors.lastname: Xing
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Wu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012503:Saponins / Q000627:therapeutic use; D013150:Spirostans / Q000737:chemistry / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D013150:Spirostans; D051028:bcl-2-Associated X Protein; C016347:deltonin; D011065:Poly(ADP-ribose) Polymerases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9