@article { author = {Hashemi, Seyed Ali and Bathaie, Seyedeh zahra and Mohagheghi, Mohammad Ali}, title = {Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines}, journal = {Avicenna Journal of Phytomedicine}, volume = {10}, number = {4}, pages = {384-397}, year = {2020}, publisher = {Mashhad University of Medical Sciences}, issn = {2228-7930}, eissn = {2228-7949}, doi = {10.22038/ajp.2019.14372}, abstract = {Objective: 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. Materials and Methods: A multi-model approach involving in vivo, in vitro and in silico 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. Results: 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 (ΔG0=-6.6 kcal/mol) than simvastatin (ΔG0 =-6.0 kcal/mol). Conclusion: 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. In silico analysis indicated Crt binding in the HMGCR active site.}, keywords = {Lipid Content,4T1-induced Breast Tumor,MDA-MB-231,MCF-7,HMGCR,Docking}, url = {https://ajp.mums.ac.ir/article_14372.html}, eprint = {https://ajp.mums.ac.ir/article_14372_fd193572464a065ed116f25b4127435b.pdf} }