Breast Cancer Research and Treatment

, Volume 135, Issue 2, pp 445–458 | Cite as

Cucurbitacin E inhibits breast tumor metastasis by suppressing cell migration and invasion

  • Tao Zhang
  • Jingjie Li
  • Yanmin Dong
  • Dong Zhai
  • Li Lai
  • Fujun Dai
  • Huayun Deng
  • Yihua Chen
  • Mingyao Liu
  • Zhengfang Yi
Preclinical Study

Abstract

Tumor metastasis is the main cause of cancer-related deaths of patients. Breast cancer is highly malignant with considerable metastatic potential, which urges the necessity for developing novel potential drug candidate to prevent tumor metastasis. Here, we report our finding with Cucurbitacin E (CuE, α-elaterin), a tetracyclic triterpenes compound isolated from Cucurbitaceae. The potency of CuE on breast cancer metastasis inhibition was assessed in vivo and in vitro. In our animal experiments, intraperitoneal administrations of CuE significantly inhibited breast tumor metastasis to the lung without affecting apoptosis or proliferation of inoculated 4T1 and MDA-MB-231 breast cancer cells. Treatment of metastatic breast tumor cells with CuE markedly blocked tumor cell migration and invasion in vitro. Subsequent studies showed that CuE impaired Arp2/3-dependent actin polymerization and suppressed Src/FAK/Rac1/MMP involved pathway. Overall, our data demonstrate that CuE blocks breast cancer metastasis by suppressing tumor cell migration and invasion. We provide first evidence of a novel role for CuE as a potential candidate for treating breast cancer metastasis.

Keywords

Cucurbitacin E Breast cancer Metastasis Migration Invasion 

Abbreviations

CuE

Cucurbitacin E

FAK

Focal adhesion kinase

ARP2/3

Actin-related protein 2/3

MMP

Matrix metalloproteinase

JNK

c-Jun N-terminal kinases

TIMP

Tissue inhibitor of MMP

H&E

Hematoxylin and eosin

IVIS

In Vivo Imaging System

WASP

Wiskott-Aldrich Syndrome Protein

Supplementary material

10549_2012_2175_MOESM1_ESM.doc (1.9 mb)
Supplementary material 1 (DOC 1922 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Tao Zhang
    • 1
  • Jingjie Li
    • 1
  • Yanmin Dong
    • 1
  • Dong Zhai
    • 1
  • Li Lai
    • 1
  • Fujun Dai
    • 1
  • Huayun Deng
    • 1
  • Yihua Chen
    • 1
  • Mingyao Liu
    • 1
    • 2
  • Zhengfang Yi
    • 1
  1. 1.Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiChina
  2. 2.Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology and Department of Molecular and Cellular MedicineTexas A&M University Health Science CenterHoustonUSA

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