Dietary crocin reverses melanoma metastasis

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-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 g-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.

Crocin inhibits the migration, invasion, and epithelial‐mesenchymal transition of gastric cancer cells via miR‐320/KLF5/HIF‐1α signaling

“…Metastasis and EMT are closely related to the poor prognosis of patients with gastric cancer (Cui et al, ; Zhou et al, ). Bakshi, Hakkim, Sam, Javid, and Rashan () demonstrated that dietary crocin reversed melanoma metastasis in a mouse model. Crocin also showed antimetastatic effects in 4T1 breast cancer cells through interference with the Wnt/β‐catenin pathway (Arzi, Riazi, Sadeghizadeh, Hoshyar, & Jafarzadeh, ).…”

“…Metastasis and EMT are closely related to the poor prognosis of patients with gastric cancer (Cui et al, 2018;Zhou et al, 2017). Bakshi, Hakkim, Sam, Javid, and Rashan (2017) demonstrated that dietary crocin reversed melanoma metastasis in a mouse model.…”

Effect of crocin on PKHD1 and KLLN genes expression in kidney tissue of female rats treated with cadmium

“…According to research, crocin is a compound with high antioxidant and anti-inflammatory properties that, due to its positive properties, can reduce the production of free radicals and greatly protects the cells and tissues involved (Bakshi et al, 2017). So, since the phenomenon of apoptosis abolished many in cancer cells, the use of crocin is likely to induce the apoptotic process to cause premature death of cancer cells (Hoshyar et al, 2017).…”

“…Most herbal research today relates to the healing and therapeutic effects of traditional herbs that have long been used in societies. One of these plants, which has multiple scientific articles on its properties and importance in published scientific journals, is the saffron plant from the Iridaceae family with various compounds and antioxidant properties, one of the compounds of interest to researchers in saffron is crocin (Bakshi et al, 2017). Crocin is a carotenoid chemical compound with very high antioxidant properties (Bakshi et al, 2017) and has anti-inflammatory properties (Bakhtiary et al, 2014;Bakshi et al, 2017).…”

Advances on the anti-tumor mechanisms of the carotenoid Crocin

“…matrix metalloproteinase (MMP) 9 is a matrix protein associated with extracellular matrix (ECM) remodeling that promotes tumor progression and regulates the activity of cell adhesion molecules and cytokines ( Joseph et al, 2020 ). Bakshi et al (2017b) found that crocin inhibited the expression of MMP-2, MMP-9, ERK-2, K-ras and VEGF, and attenuated the ability of melanoma cells (B16F-10) to invade, migrate, and adhere by upregulating the expression of E-cadherin. Human gastric mucosal epithelial cells (GES-1) have malignant cell characteristics such as proliferation, apoptosis, and metastatic ability.…”