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....
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Mashhad University of Medical Sciences
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doaj-f63da9ad6cb54827a0d477ee192eb4372020-11-25T03:48:31ZengMashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-79302228-79492020-07-0110438439710.22038/ajp.2019.1437214372Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell linesSeyed Ali Hashemi0Seyedeh zahra Bathaie1Mohammad Ali Mohagheghi2Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranCancer Research Center of Cancer Institute, Imam Khomeini Hospital, Tehran University of Medical Science, Tehran, Iran.<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.http://ajp.mums.ac.ir/article_14372_fd193572464a065ed116f25b4127435b.pdflipid content4t1-induced breast tumormda-mb-231mcf-7hmgcrdocking |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Seyed Ali Hashemi Seyedeh zahra Bathaie Mohammad Ali Mohagheghi |
spellingShingle |
Seyed Ali Hashemi Seyedeh zahra Bathaie Mohammad Ali Mohagheghi Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines Avicenna Journal of Phytomedicine lipid content 4t1-induced breast tumor mda-mb-231 mcf-7 hmgcr docking |
author_facet |
Seyed Ali Hashemi Seyedeh zahra Bathaie Mohammad Ali Mohagheghi |
author_sort |
Seyed Ali Hashemi |
title |
Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines |
title_short |
Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines |
title_full |
Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines |
title_fullStr |
Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines |
title_full_unstemmed |
Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines |
title_sort |
crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines |
publisher |
Mashhad University of Medical Sciences |
series |
Avicenna Journal of Phytomedicine |
issn |
2228-7930 2228-7949 |
publishDate |
2020-07-01 |
description |
<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. |
topic |
lipid content 4t1-induced breast tumor mda-mb-231 mcf-7 hmgcr docking |
url |
http://ajp.mums.ac.ir/article_14372_fd193572464a065ed116f25b4127435b.pdf |
work_keys_str_mv |
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