Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines

• Published in: Avicenna journal of phytomedicine Vol. 10; no. 4; pp. 384 - 397
• Main Authors: Hashemi, Seyed Ali, Bathaie, Seyedeh Zahra, Mohagheghi, Mohammad Ali
• Format: Journal Article
• Language: English
• Published: Iran Mashhad University of Medical Sciences 01.07.2020
• Subjects: 4t1-induced breast tumor; docking; hmgcr; lipid content; mcf-7; mda-mb-231; Original; Docking; 4T1-induced breast tumor MDA-MB-231; Binding affinity; HMGCR; MCF-7; Lipid content
• ISSN: 2228-7930; 2228-7949
• DOI: 10.22038/AJP.2019.14372

Inhibition of lipid metabolism in breast cancer has been suggested as an effective approach for cancer therapy. Saffron-derived crocetin (Crt) and crocin (Cro) with the known anticancer activity, have shown hypolipidemic effect in diabetes and atherosclerosis. Here, we investigated the effect of Crt/Cro on lipid content in breast cancer. A multi-model approach involving and studies was applied. The 4T1-induced breast cancer in mice was used to investigate the effect of Crt/Cro on cholesterol (Chl) and triglyceride (TG) levels in serum and tumor tissues. The Chl/TG levels were also assessed in the cytosol of MDA-MB-231 and MCF-7 breast cancer cell lines 6, 12 and 24 hr after Crt/Cro treatment. The interaction between Crt/Cro and hydroxymethylglutaryl coenzyme A reductase (HMGCR) was also computed by docking analysis. Crt reduced both serum (p=0.003) and tumor (p=0.011) Chl and TG (p=0.001) levels in mice. Cro reduced TG levels in tumor (p=0.014) and serum (p=0.002) and Chl level in tumor (p=0.013) tissues. Crt reduced both Chl and TG in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Cro reduced both Chl and TG in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Crt binds to the active site of HMGCR with higher affinity (ΔG =-6.6 kcal/mol) than simvastatin (ΔG =-6.0 kcal/mol). Crt and Cro effectively decreased Chl/TG content in the sera of tumor bearing mice, in breast tumors and breast cancer cell lines. Crt showed a higher hypolipidemic potential than Cro. analysis indicated Crt binding in the HMGCR active site.