cyclin-d1 and crocin

We previously showed the anticancer effect of crocin, a saffron carotenoid, in both breast and gastric cancers in animal models, but its mechanism of action is not clearly known, yet. In this study, the effect of crocin on cell cycle regulators is investigated. Female Wistar Albino rats were divided into two groups, with or without N-nitroso-N-methylurea (NMU) injection. After tumor formation, each group of rats was divided into two subgroups, receiving crocin or vehicle only. After 5 weeks, the rats were sacrificed and the tumors were retained for pathologic investigation and determination of the parameters. Before crocin treatment, the tumor volumes were 13.27±3.77 and 12.37±1.88, but at the end of the experiment, they were 23.66±8.82 and 11.91±2.27 in the control and crocin-treated groups, respectively. Pathologic investigation indicated the adenocarcinoma induction by NMU. Reverse transcription-polymerase chain reaction and Western blot analysis showed overexpression of cyclin D1 and p21(Cip1) in the NMU-induced breast tumors; however, the expression of both of them suppressed by crocin treatment. The previous studies indicated that crocin induces apoptosis in tumor tissue. In this study, we show that it also suppresses tumor growth and induces cell cycle arrest by downregulation of cyclin D1. In addition, crocin suppressed p21(Cip1) in a p53-dependent manner.

Topics: Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Carotenoids; Cell Cycle; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Female; Gene Expression Regulation, Neoplastic; Genes, p53; Mammary Neoplasms, Experimental; Methylnitrosourea; Rats, Wistar

To investigate the proliferation, apoptosis and mechanisms on T24 cell of transitional cell carcinoma of bladder (TCCB) by crocin.. MTT assay was used to evaluate the proliferation of T24 cells. The changes of cell cycle and cell apoptotic percentage were measured by flow cytometry. T24 cells were inoculated into BALB/c nude mice to establish model of carcinoma of bladder. The mice were randomly divided into control group and experimental group. After treatment with 50 mmol x L(-1) crocin, the inhibited growth of tumor was observed. Electronic microscope was used to observe the morphological changes. The expressions of Bcl-2, Bax, Survivin and Cyclin D1 were detected by immunohistochemistry.. The growth of T24 cells was remarkably inhibited after treatment of crocin. Flow cytometric profiles revealed that crocin led to the increase of the cells in G0/G1 phase, the percentage of cell apoptosis was also increased. Crocin could inhibit the growth of BALB/c xenograft tumor. The morphology changes of cell apoptosis were observed. Bcl-2, Cyclin D1 and survivin expressions determined by immunohistochemical staining were down-regulated after treatment with Bax expression up-regulated.. Crocin exerts both in vitro and in vivo anti-cancer effect on TCCB T24 cell line. The mechanisms may change tumour cell cycle and induce tumour cell apoptosis by down-regulating the expression of Bcl-2, Survivin, Cyclin D1 and up-regulating the expression of Bax.

Topics: Animals; Apoptosis; Carcinoma, Transitional Cell; Carotenoids; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Inhibitor of Apoptosis Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron, Transmission; Microtubule-Associated Proteins; Proto-Oncogene Proteins c-bcl-2; Repressor Proteins; Survivin; Transplantation, Heterologous; Urinary Bladder Neoplasms