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. 2017 Nov 1;32(1):39-50.
doi: 10.7555/JBR.31.20160120. Online ahead of print.

Dietary Crocin Reverses Melanoma Metastasis

Hamid A Bakshi  1   2 , Faruck Lukmanul Hakkim  3 , Smitha Sam  2 , Farideh Javid  1 , Luay Rashan
Affiliations

Dietary Crocin Reverses Melanoma Metastasis

Hamid A Bakshi et al. J Biomed Res. .

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 (g-GGT), sialic acid, tumor necrosis factor alpha (TNF-a), 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 metalloproteases (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 h 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 andg-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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Figures

Fig.1
Fig.1
Effect of dietary crocin on lung metastasis.
Fig.2
Fig.2
Effect of dietary crocin on mean survival time and body weight.
Fig.3
Fig.3
Effect of dietary crocin on the lung biochemical parameters.
Fig.4
Fig.4
Effect of dietary crocin on the serum γ-GT and sialic acid levels in metastasis bearing animals.
Fig.5
Fig.5
Effect of dietary crocin on adhesion, invasion, migration and E-cadherin expression.
Fig.6
Fig.6
Effect of dietary crocin on the TIMP-1 level, MMP-2 and MMP-9, VEGF, ERK, and K-Ras expression in metastasis bearing animals.
Fig.7
Fig.7
Effect of dietary crocin on serum TNF-α, IL-6, IL-2 and IL-10 in in metastatic bearing animals.
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