Planta Med 2011; 77(2): 146-151
DOI: 10.1055/s-0030-1250178
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Crocetin Inhibits Invasiveness of MDA‐MB‐231 Breast Cancer Cells via Downregulation of Matrix Metalloproteinases

Dimitra G. Chryssanthi1 , Petros G. Dedes2 , Nikos K. Karamanos2 , Paul Cordopatis1 , Fotini N. Lamari1
  • 1Department of Pharmacy, Laboratory of Pharmacognosy & Chemistry of Natural Products, University of Patras, Rion, Greece
  • 2Department of Chemistry, Laboratory of Biochemistry, University of Patras, Rion, Greece
Further Information

Publication History

received April 22, 2010 revised June 21, 2010

accepted July 1, 2010

Publication Date:
27 August 2010 (online)

Abstract

Crocetin is a carotenoid dicarboxylic acid which, in nature, is esterified with glucose or gentiobiose units forming the crocins, abundant components of saffron (a spice with many reputed medicinal uses). We have previously reported that saffron, crocins and crocetin inhibit breast cancer cell proliferation. In order to further study the effect of crocetin on breast cancer cells, we used the highly invasive MDA‐MB‐231 cells and measured the viability with the WST-1 assay and the invasiveness through a reconstituted basement membrane. After 24 h incubation, crocetin significantly inhibited not only proliferation but also invasion at 1 and 10 µM. Cancer invasiveness and metastasis are associated with the expression of matrix metalloproteinases (MMPs). In order to study the molecular changes of MMP expression that might accompany the observed crocetin effects, gene expression of MMPs was studied by RT‐PCR, whereas protein expression and gelatinolytic activity were determined with Western blotting and zymography, respectively. The gene and protein expression of pro-MT1-MMP and pro-MT2-MMP were greatly attenuated by both crocetin and all-trans-retinoic acid (ATRA, used as control). Incubation with 10 µM crocetin for 24 h in serum-free conditions reduced pro-MMP‐9 activity and pro-MMP‐2/MMP‐2 protein levels. When cultured in media with sera 2 and 5 %, crocetin at 10 μΜ also reduced gelatinase activity. The above findings show that crocetin, the main metabolite of crocins, inhibits MDA‐MB‐231 cell invasiveness via downregulation of MMP expression.

References

Dr. Fotini N. Lamari

Department of Pharmacy
Laboratory of Pharmacognosy & Chemistry of Natural Products
University of Patras

26504 Rion

Greece

Phone: + 30 26 10 96 93 35

Fax: + 30 26 10 99 32 78

Email: flam@upatras.gr