Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model

Abstract

Crocetin, a carotenoid compound derived from saffron, has long been used as a traditional ancient medicine against different human diseases including cancer. The aim of the series of experiments was to systematically determine whether crocetin significantly affects pancreatic cancer growth both in vitro and/or in vivo. For the in vitro studies, first, MIA-PaCa-2 cells were treated with crocetin and in these sets of experiments, a proliferation assay using H 3 -thymidine incorporation and flow cytometric analysis suggested that crocetin inhibited proliferation. Next, cell cycle proteins were investigated. Cdc-2, Cdc-25C, Cyclin-B1, and epidermal growth factor receptor were altered significantly by crocetin. To further confirm the findings of inhibition of proliferation, H 3 -thymidine incorporation in BxPC-3, Capan-1, and ASPC-1 pancreatic cancer cells was also significantly inhibited by crocetin treatment. For the in vivo studies, MIA-PaCa-2 as highly aggressive cells than other pancreatic cancer cells used in this study were injected into the right hind leg of the athymic nude mice and crocetin was given orally after the development of a palpable tumor. The in vivo results showed significant regression in tumor growth with inhibition of proliferation as determined by proliferating cell nuclear antigen and epidermal growth factor receptor expression in the crocetin-treated animals compared with the controls. Both the in vitro pancreatic cancer cells and in vivo athymic nude mice tumor, apoptosis was significantly stimulated as indicated by Bax/Bcl-2 ratio. This study indicates that crocetin has a significant antitumorigenic effect in both in vitro and in vivo on pancreatic cancer. [Mol Cancer Ther 2009;8(2):315 -23]

Crocetin induces apoptosis of BGC-823 human gastric cancer cells

“…Among the cytotoxicity detection experiments, crocetin revealed significant antiproliferative effects on the BGC-823 cells in a dose-and time-dependent manner. It is noteworthy that accumulated data concerning the toxic effect of crocetin has been reported, but there are different standpoints with regard to its effect (14). However, one previous in vitro study observed that crocetin had no cytotoxic effect in the normal cells (23).…”

“…Crocetin, a major active ingredient of saffron extract, has been revealed to possess potent antiproliferative and antioxidative characteristics. Moreover, the antitumor activity of crocetin has been observed to enhance the apoptosis of several types of cancer cells in vitro and inhibit the growth of tumors in vivo, including human liver (12), colorectal (13), pancreatic (14) and breast (15) cancer cells.…”

Reduction of metabolic and behavioral signs of acute stress in male Wistar rats by saffron water extract and its constituent safranal

“…The plant was used as an aphrodisiac, antispasmodic, and expectorant in folk medicine (Abdullaev, 1993;Abdullaev & Espinosa-Aguirre, 2004). In modern medicine, antimicrobial (Aung et al, 2007) and anticancer (Aung et al, 2007;Das et al, 2009;Dhar et al, 2009) effects have been described for its extract. It is now clear that saffron water or alcohol extracts may have anti-anxiety (Pitsikas et al, 2008;Hosseinzadeh & Noraei, 2009) and antidepressant effects (Akhondzadeh et al, 2004;Moshiri et al, 2006;Akhondzadeh Basti et al, 2007).…”

Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L.): a review

“…Many studies have demonstrated various pharmacological effects of saffron and or its important compounds including antioxidant activity, anti tumor, memory and learning enhancing, treatment of hepatic disorders, anti inflammatory, anti depressant and insulin resistant reducing (Sanchez-Vioque et al 2012;Makhlouf et al 2011;Umigai et al 2011;Ghadrdoost et al 2011;Amin et al 2011;Dhar et al 2009;Nkhaei et al 2008;Ochiai et al 2007;Soeda et al 2007;Abdullaev and Espinosa-Aguirre 2004). All these properties have been attributed to the stigmas, the sole commercially valuable part of the plant whereas other parts of the plant have been much less studied.…”