DT-13, a saponin of dwarf lilyturf tuber, exhibits anti-cancer activity by down-regulating C-C chemokine receptor type 5 and vascular endothelial growth factor in MDA-MB-435 cells.
OBJECTIVE
To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action.


METHODS
MDA-MB-435 cell proliferation, migration, and adhesion were performed to assess the anticancer activity of DT-13, a saponin from Ophiopogon japonicus, in vitro. In addition, the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice; mRNA levels of vascular endothelial growth factor (VEGF), C-C chemokine receptor type 5 (CCR5) and hypoxia-inducible factor 1α (HIF-1α) were evaluated by real-time quantitative PCR; and CCR5 protein levels were detected by Western blot assay.


RESULTS
At 0.01 to 1 μmol·L(-1), DT-13 inhibited MDA-MB-435 cell proliferation, migration, and adhesion significantly in vitro. DT-13 reduced VEGF and CCR5 mRNAs, and decreased CCR5 protein expression by down-regulating HIF-1α. In addition, DT-13 inhibited MDA-MB-435 cell lung metastasis, and restricted tumor growth slightly in vivo.


CONCLUSIONS
DT-13 inhibited MDA-MB-435 cell proliferation, adhesion, and migration in vitro, and lung metastasis in vivo by reducing VEGF, CCR5, and HIF-1α expression.
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Zhao
Z
Ren-Ping
Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
Lin
L
Sen-Sen
Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China; Department of Complex Prescription of Traditional Chinese Medicine, School of Chinese Material Medicine, China Pharmaceutical University, Nanjing 210009, China.
Sheng-Tao
ST
Yuan
Department of Complex Prescription of Traditional Chinese Medicine, School of Chinese Material Medicine, China Pharmaceutical University, Nanjing 210009, China.
Bo-Yang
BY
Yu
Department of Molecular Physiology, University of Saarland, 66421 Homburg, Germany.
Xian-Shu
XS
Bai
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpusunli@126.com.
Li
L
Sun
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, China. Electronic address: drugscreen@163.com.
Lu-Yong
LY
Zhang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D065100:CCR5 Receptor Antagonists; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D031424:Liriope Plant / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D035281:Plant Tubers / Q000737:chemistry*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D065100:CCR5 Receptor Antagonists; D004365:Drugs, Chinese Herbal; D019713:Receptors, CCR5; D012503:Saponins; D042461:Vascular Endothelial Growth Factor A
Anticancer activity; CCR5; DT-13; HIF-1α; Ophiopogon japonicus; R285; Saponin; VEGF