Dietary crocin reverses melanoma metastasis

Hamid Bakshi, Faruck Hakkim, Smitha Sam, Farideh Javid, Lucy Rashan

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models. However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melanoma metastatic model was developed by tail vein injection of B16F-10 cells in to C57BL/6 mice. Metastatic mice treated with two different doses of crocin (250 and 500 μg/kg of bodyweight) for 10 days and parameters such as lung metastasis inhibition, mean survival time, lung hydroxyproline, uronic acid and hexosamine levels were analyzed after 21 days of treatment. Then blood was collected and serum gamma glutamyl transpeptidase (γ-GGT), sialic acid, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), IL-6, IL-2, and TIMP-1 levels were measured. Further, a lung histological examination was done in crocin treated metastatic mice. Subsequently hallmark metastatic parameters such as matrix metalloproteinases (MMPs), extracellular regulated kinase 2 (ERK2), vascular endothelial growth factor (VEGF), and K-ras gene expression were investigated in the lungs of crocin treated metastatic mice. Further, in-vitro adhesion, invasion and migration of B16F-10 cells were examined after 24 hours of crocin (5 and 10 μg/mL) treatment. Administration of crocin to tumor bearing C57BL/6 mice reduced the lung metastasis by 85%. Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and γ-GGT in metastatic control were found to be significantly reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9, ERK-2, K-ras, and VEGF. Crocin reduced the ability of B16F-10 cells invasion (P < 0.05), migration (P < 0.05) and adhesion by upregulating E-cadherin expression. In conclusion, crocin elicited marked anti-metastatic potential by regulating the metastasis induced biomarkers.

Original languageEnglish
Pages (from-to)39-50
Number of pages12
JournalJournal of Biomedical Research
Volume32
Issue number1
Early online date10 Sep 2017
DOIs
Publication statusPublished - 18 Jan 2018

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Melanoma
Neoplasm Metastasis
Lung
Uronic Acids
Hexosamines
Hydroxyproline
N-Acetylneuraminic Acid
Inbred C57BL Mouse
Vascular Endothelial Growth Factor A
Tumors
crocin
Bearings (structural)
Adhesion
Tissue Inhibitor of Metalloproteinase-1
ras Genes
gamma-Glutamyltransferase
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Biomarkers
Cadherins

Cite this

Bakshi, Hamid ; Hakkim, Faruck ; Sam, Smitha ; Javid, Farideh ; Rashan, Lucy. / Dietary crocin reverses melanoma metastasis. In: Journal of Biomedical Research. 2018 ; Vol. 32, No. 1. pp. 39-50.
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abstract = "Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models. However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melanoma metastatic model was developed by tail vein injection of B16F-10 cells in to C57BL/6 mice. Metastatic mice treated with two different doses of crocin (250 and 500 μg/kg of bodyweight) for 10 days and parameters such as lung metastasis inhibition, mean survival time, lung hydroxyproline, uronic acid and hexosamine levels were analyzed after 21 days of treatment. Then blood was collected and serum gamma glutamyl transpeptidase (γ-GGT), sialic acid, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), IL-6, IL-2, and TIMP-1 levels were measured. Further, a lung histological examination was done in crocin treated metastatic mice. Subsequently hallmark metastatic parameters such as matrix metalloproteinases (MMPs), extracellular regulated kinase 2 (ERK2), vascular endothelial growth factor (VEGF), and K-ras gene expression were investigated in the lungs of crocin treated metastatic mice. Further, in-vitro adhesion, invasion and migration of B16F-10 cells were examined after 24 hours of crocin (5 and 10 μg/mL) treatment. Administration of crocin to tumor bearing C57BL/6 mice reduced the lung metastasis by 85{\%}. Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and γ-GGT in metastatic control were found to be significantly reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9, ERK-2, K-ras, and VEGF. Crocin reduced the ability of B16F-10 cells invasion (P < 0.05), migration (P < 0.05) and adhesion by upregulating E-cadherin expression. In conclusion, crocin elicited marked anti-metastatic potential by regulating the metastasis induced biomarkers.",
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Dietary crocin reverses melanoma metastasis. / Bakshi, Hamid; Hakkim, Faruck; Sam, Smitha; Javid, Farideh; Rashan, Lucy.

In: Journal of Biomedical Research, Vol. 32, No. 1, 18.01.2018, p. 39-50.

Research output: Contribution to journalArticle

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T1 - Dietary crocin reverses melanoma metastasis

AU - Bakshi, Hamid

AU - Hakkim, Faruck

AU - Sam, Smitha

AU - Javid, Farideh

AU - Rashan, Lucy

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AB - Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models. However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melanoma metastatic model was developed by tail vein injection of B16F-10 cells in to C57BL/6 mice. Metastatic mice treated with two different doses of crocin (250 and 500 μg/kg of bodyweight) for 10 days and parameters such as lung metastasis inhibition, mean survival time, lung hydroxyproline, uronic acid and hexosamine levels were analyzed after 21 days of treatment. Then blood was collected and serum gamma glutamyl transpeptidase (γ-GGT), sialic acid, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), IL-6, IL-2, and TIMP-1 levels were measured. Further, a lung histological examination was done in crocin treated metastatic mice. Subsequently hallmark metastatic parameters such as matrix metalloproteinases (MMPs), extracellular regulated kinase 2 (ERK2), vascular endothelial growth factor (VEGF), and K-ras gene expression were investigated in the lungs of crocin treated metastatic mice. Further, in-vitro adhesion, invasion and migration of B16F-10 cells were examined after 24 hours of crocin (5 and 10 μg/mL) treatment. Administration of crocin to tumor bearing C57BL/6 mice reduced the lung metastasis by 85%. Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and γ-GGT in metastatic control were found to be significantly reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9, ERK-2, K-ras, and VEGF. Crocin reduced the ability of B16F-10 cells invasion (P < 0.05), migration (P < 0.05) and adhesion by upregulating E-cadherin expression. In conclusion, crocin elicited marked anti-metastatic potential by regulating the metastasis induced biomarkers.

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