Crocetin regulates cell cycle progression in N-nitroso-Nmethylurea(NMU)-induced breast cancer in rat: cyclin D1 suppression, p21Cip1 and p53 induction

S. Zahra Bathaie; Mahboobeh Ashraf; Mahshid Azizian; Narges Khademian; Saeid Abroun

doi:10.18502/abi.v2i1.16244

S. Zahra Bathaie Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Mahboobeh Ashraf Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Mahshid Azizian Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Narges Khademian Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Saeid Abroun Department of Hematology Faculty of Medical Sciences, Tarbiat Modares University.

DOI: https://doi.org/10.18502/abi.v2i1.16244

Keywords: Saffron Carotenoid; Cell Cycle; p53; Cyclin D1; p21; p27.

Abstract

Objectives: Crocetin, a saffron-derived carotenoid, inhibits tumor growth in some cancer types. However, its mechanism of action still needs to be clearly understood. Here, the Crocetin effect on the expression of some cell cycle regulators was investigated.

Methods: The N-nitroso-N-methylurea (NMU)-induced rat mammary carcinomas were induced in a group of 35-day-old female Wistar Albino rats. Then, the expression of several cell cycle regulators was studied using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. After the tumor appearance, these rats were treated with Crocetin through weekly, intraperitoneal injections of 100 mg/kg body weight for four weeks. A control group has received the vehicle only. In the end, rats were sacrificed, and tumors were divided into two parts. A part was for pathologic investigation, and a part was retained at -70 °C to determine desired parameters.

Results: Before Crocetin treatment, the tumor volumes were 13.27 ± 3.77 and 9.44 ± 4.39 cm3 , which was changed to 23.66 ± 8.82 and 4.71 ± 2.44 cm3 at the end of the experiment in the untreated and treated groups, respectively. The results showed that Crocetin markedly decreased the increased expression of cyclin D1 due to NMU administration. However, it further increased the expression of p53 and p21Cip1, with no significant effect on p27Kip1 expression. We previously showed Crocin-induced cell cycle arrest through a p53-dependent mechanism.

Conclusion: Crocetin induced the cell cycle arrest in NMU-induced breast cancer in rats through a p53-independent mechanism. It is the second mechanism additional to apoptosis induction in cancer cells.