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Chin J Nat Med. 2014 Jan;12(1):24-9. doi: 10.1016/S1875-5364(14)60005-4.

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.

Author information

1
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
2
Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
3
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.
4
Department of Complex Prescription of Traditional Chinese Medicine, School of Chinese Material Medicine, China Pharmaceutical University, Nanjing 210009, China.
5
Department of Molecular Physiology, University of Saarland, 66421 Homburg, Germany.
6
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpusunli@126.com.
7
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.

Abstract

AIM:

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.

CONCLUSION:

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.

KEYWORDS:

Anticancer activity; CCR5; DT-13; HIF-1α; Ophiopogon japonicus; R285; Saponin; VEGF

PMID:
24484593
DOI:
10.1016/S1875-5364(14)60005-4
[Indexed for MEDLINE]
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