Crocetin alters the gene expression pattern of metalloproteinases and their inhibitors in breast cancer cells MDA-MB-231

Crocus sativus is cultivated in Greece at the area of Krokos in Kozani (West Macedonia) for the exquisite flavoring and coloring properties of its styles (saffron). Saffron has long been used in traditional medicine. Modern studies have shown an inhibitory effect of its extract against various cancer cells [1]. Recently our research group has reported that saffron constituents inhibit breast cancer cell proliferation at high concentrations [2]. Cancer growth, invasiveness and metastasis have been associated with overexpression of metalloproteinases (MMPs). In the present study, the effect of crocetin, the active metabolite of C. sativus crocins, on the expression of MMPs and their tissue inhibitors (TIMPs) was studied in the highly invasive epithelial breast cancer cells, MDA-MB-231. Gene expression studies were performed following cell cultures for 24h in serum-free conditions, RNA isolation, reverse transcription and polymerase chain reaction. Results have shown that both crocetin at 1µM and 10µM and all-trans-retinoic acid at 10µM induce alterations in the gene expression pattern of MMPs and their TIMPs, although they do not affect cell proliferation at these concentrations. In particular, significantly lower levels of MT-MMPs and higher levels of TIMP-3 mRNA were recorded. Only pro-MMP-9 was recorded in zymographs. These results suggest that saffron might be of value for suppression of invasiveness of breast cancer and deserves further investigation.

Acknowledgement: The financial support from the Research Committee of the University of Patras under the research grant „K. Karatheodoris“ is acknowledged.

References 1. Abdullaev, F.I., Espinosa-Aguirre, J.J. (2004) Cancer Detect Prev 28: 426–432.

2. Chryssanthi, D.G. et al. (2007) Anticancer Research 27: 357–362