Saffron is a spice with preventive and curative effects. This study aimed to review the toxicity of saffron extract and its constituents on normal and cancer cells.

We searched the PubMed, Science direct, SID and Magiran databases up to November 2015 using the following key words: toxicity, saffron, crocin, crocetin, safranal, cancer. Finally, 73 English and 5 Persian articles were selected to be recruited to be reviewed.

Saffron has selective toxicity against cancer cells, through inhibition of RNA and DNA synthesis and increasing apoptosis. Crocin has been considered as the most important anticancer agent of saffron that plays a role in gene expression and apoptosis in cancer cells. Crocetin has an inhibitory effect on the cancer cells growth that may be due to reduced synthesis of DNA, RNA and protein in neoplastic cells, RNA polymerase II inhibition, and interaction with histone H1 and H1-DNA structures. Saffron and its crocin and crocetin have also shown anticancer and cancer-preventive effects in animal models of cancer. Safranal also has shown antitumor activity with low toxicity. On the other hand, the lethal dose of 50% (LD50) for the saffron and its constituents against normal cells can be very high.

In conclusion, emerging evidence suggests that saffron extract and its crocin, crocetin and safranal have a selective toxicity effects against cancer cells and also may have cancer preventive functions. However, Saffron and its constituent's toxicity against normal cells is negligible and they are even non-toxic in oral administration.