Antitumor Effects of Saffron-Derived Carotenoids in Prostate Cancer Cell Models

Abstract

Crocus sativus L. extracts (saffron) are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles. We have recently reported that saffron (SE) and crocin (CR) exhibit anticancer activity by promoting cell cycle arrest in prostate cancer (PCa) cells. It has also been demonstrated that crocetin esters are produced after SE gastrointestinal digestion by CR hydrolysis. The aim of the present report was to investigate if SE, crocetin (CCT), and CR affected in vivo tumor growth of two aggressive PCa cell lines (PC3 and 22rv1) which were xenografted in male nude mice treated by oral gavage with SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher when compared to CR and SE and treatments reverted the epithelial-mesenchymal transdifferentiation (EMT) as attested by the significant reduction of N-cadherin and beta-catenin expression and the increased expression of E-cadherin. Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through the downmodulation of metalloproteinase and urokinase expression/activity suggesting that these agents may affect metastatic processes. Our findings suggest that CR and CCT may be dietary phytochemicals with potential antitumor effects in biologically aggressive PCa cells.

Crocin inhibits the migration, invasion, and epithelial‐mesenchymal transition of gastric cancer cells via miR‐320/KLF5/HIF‐1α signaling

“…N = 5, each value represents mean ± SD, *p < 0.05 versus the NC mimic group. GAPDH: glyceraldehyde 3-phosphate dehydrogenase; HIF-1α: hypoxia-inducible factor-1α; KLF5: Krüppel-like factor 5; miR: microRNA; mut: mutant; NC: negative control; mRNA: messenger RNA; PCR: polymerase chain reaction; SD: standard deviation; wt: wild-type Evidence has accumulated that crocin has anticancer activities in many cancers (Festuccia et al, 2014;Hire et al, 2017;Mollaei et al, 2017). Its effect in gastric cancer is not fully understood, although a previous study found that it could trigger apoptosis of gastric adenocarcinoma AGS cells by increasing the Bax/Bcl-2 ratio (Hoshyar et al, 2013).…”

Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells

“…Crocin inhibits tumor growth and its spread in several forms of cancer including colorectal7, pancreatic89, breast10, and prostate cancers11, as well as chronic myelogenous12 and other leukemias1314 indicating its potential use as a cancer chemotherapeutic and cancer preventive agent.…”

A comprehensive review on anticancer mechanisms of the main carotenoid of saffron, crocin

“…In this study, EMT was evaluated under crocin treatment in vivo . For this aim, tumour growth of aggressive cancer cell lines (such as PC3 and 22rv1) was xenografted in nude mice treated by oral crocin . Results showed that the significant reduction in N‐cadherin and beta‐catenin expression and the increased expression of E‐cadherin led to EMT reversion …”

“…analysed the immunohistochemistry expression of proteases involved in the migratory and invasive properties of the mentioned xenografts after treatment with 0.4 m m crocin. Their results showed that crocin inhibits cell invasion through modulation of metalloproteinases and urokinase expression or activity …”