Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines
<strong>Objective:</strong> 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....
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Mashhad University of Medical Sciences
2020-07-01
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| Series: | Avicenna Journal of Phytomedicine |
| Subjects: | |
| Online Access: | http://ajp.mums.ac.ir/article_14372_fd193572464a065ed116f25b4127435b.pdf |
| Summary: | <strong>Objective:</strong> 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.<br /> <strong>Materials and Methods:</strong> A multi-model approach involving <em>in vivo, in vitro </em>and<em> in silico </em>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.<br /> <strong>Results: </strong>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<sup>0</sup>=-6.6 kcal/mol) than simvastatin (ΔG<sup>0 </sup>=-6.0 kcal/mol).<br /> <strong>Conclusion:</strong> 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. <em>In silico</em> analysis indicated Crt binding in the HMGCR active site. |
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| ISSN: | 2228-7930 2228-7949 |