Crocus Sativus Stigma Extract and Its Major Constituent Crocin Possess Significant Antiproliferative Properties Against Human Prostate Cancer

Abstract

In this study, we investigated the antiproliferative effects of saffron extract (SE) and its major constituent crocin on 5 different malignant and 2 nonmalignant prostate cancer cell lines. Using high performance liquid chromatography (HPLC), the purity and content of crocin were determined. All cells were incubated with different concentrations of SE or crocin for 48 h. Cell cycle and apoptosis were also evaluated. In a time- and concentration-dependent manner, both SE and crocin reduced cell proliferation in all malignant cell lines with IC50 values ranging between 0.4 and 4 mg/ml for SE and between 0.26 and 0.95 mM/ml for crocin. Nonmalignant cells were not affected. Flow cytometry profiles revealed that most cells were arrested at G0/G1 phase with a significant presence of apoptotic cells. Western blot analysis revealed that the expression of Bcl-2 was strikingly downregulated, whereas Bax was upregulated. Analysis of caspase activity indicated a caspase-dependent pathway with involvement of caspase-9 activation, suggesting an intrinsic pathway. Based on these findings, it can be concluded that both SE and crocin can inhibit cell proliferation, arrest cell cycle progression, inducing apoptosis in prostate cancer. Consequently, these agents could potentially be used as a chemopreventive as well as a chemotherapeutic agent for prostate cancer management.

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

“…We observed that SE, CR, and CCT reduced tumor growth in both PC3 and 22rv1 (Figures 1 and 2) xenografts confirming our previous in vitro data [12]. In the PC3 in vivo model, the tumor mass (Figures 1(a)–1(c) and Table 1) was, respectively, reduced by 18% ( P > 0.05), 38% ( P < 0.05), and 75% ( P < 0.001) after SE, CR, and CCT treatment with respect to controls.…”

“…The bitter taste of saffron is attributed to picrocrocin, a degradation product of the zeaxanthin carotenoid and also a monoterpene glycoside precursor of safranal. Safranal is an aromatic aldehyde that is the main component of plant volatile oil [12, 13]. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and anticancer activities of SE [11, 14–19].…”

“…We have previously demonstrated that SE and CR possessed in vitro antiproliferative/cytostatic effects in prostate cancer cells [12] with low proapoptotic activity. Here, two aggressive prostate cancer cell lines, PC3 and 22rv1, were xenografted into nude mice and tumor-bearing animals were treated by oral gavage with saffron extract (300 mg/Kg/day), crocin (200 mg/Kg/day), and crocetin (30 mg/Kg/day) after the development of palpable tumors.…”

Fertility preservation in cancer patients: attenuation of chemotherapy-induced ovarian damage by oral administration of phytochemical carotenoids in an animal model

“…Nowadays, increased rates of cure or remission obtained by anticancer treatments (29,30) @ C I C E d i z i o n i I n t e r n a z i o n a l i fects on numerous cancer types including those with high incidence in women of reproductive age, they may represent good candidates as protective compounds against chemo-induced gonadotoxicity (21,31). In this context, present findings represent the first evidence for the chemoprotective potential of natural antioxidant compounds against ovarian cytotoxicity and are consistent with previous results in the male gonad and other organs in mice (21,32,33). It is known that PFs are in a quiescent state by fine tuning of the PI3K/PTEN/Akt-FOXO3a pathway (17).…”

Saffron (Crocus sativus) and its Active Ingredients: Role in the Prevention and Treatment of Disease

“…Results based on these findings reported that crocin reduced proliferation in all malignant cells whereas nonmalignant cells were not affected at all. 75 In addition to this, another experiment was performed to investigate the chemopreventive effect of aqueous saffron. The result of the studies reported that saffron ingestion inhibited the formation of skin papillomas and simultaneously reduced their size in animals.…”