Dietary crocin reverses melanoma metastasis

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 B16 F-10 cells in to C57 BL/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-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 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 B16 F-10 cells were examined after 24 hours of crocin（5 and 10μg/mL） treatment. Administration of crocin to tumor bearing C57 BL/6 mice reduced the lung metastasis by 85%.Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and y-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 B16 F-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.

Co-delivery of TRAIL and paclitaxel by fibronectin-targeting liposomal nanodisk for effective lung melanoma metastasis treatment

Melanoma is a highly aggressive cancer which often forms metastatic tumors in the lung,leading to sharply reduced patients'survival rate.Effectively treating these tumors thus could improve late stage melanoma with lung metastasis.In this study,we fabricated a Cys-Arg-Glu-Lys-Ala with N-methylated Glu(CR(NMe)EKA)decorated disk shaped nano vehicle to co-deliver tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and paclitaxel(PTX)to lung melanoma tumor sites(TRAIL-[ND-PTX]^(CR(NMe)EKA)).These nanodisks displayed better tumor-targeting and penetration capability than spherical nanoparticles,while the fibronectin-targeting CR(NMe)EKA motif also increased the tumor accumulation of loaded drugs.The combined usage of TRAIL and PTX both killed tumor cells and reduced local nutrition supply,leading to stronger overall anti-tumor effect.This TRAIL-[ND-PTX]^(CR(NMe)EKA)system performed remarkably better than free paclitaxel and also significantly elongated survival rate of melanoma lung metastasis bearing mice,without displaying significant toxicity.Hence,this designing strategy and the fabricated nanoplatform possess potential for further development.

Melanoma:Molecular genetics,metastasis,targeted therapies,immunotherapies,and therapeutic resistance

Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s.For some patients,early diagnosis and surgical removal of melanomas is lifesaving,while other patients typically turn to molecular targeted therapies and immunotherapies as treatment options.Easy sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF,NRAS,and TERT genes,some of which can be therapeutically targeted.Though initially effective,many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory pathways.Immunotherapies represent an alternative to molecular targeted therapies.However,inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long term.As the protocol for combination therapies develop,so will our scientific understanding of the many pathways at play in the progression of melanoma.The future direction of the field may be to find a molecule that connects all of the pathways.Meanwhile,noncoding RNAs have been shown to play important roles in melanoma development and progression.Studying noncoding RNAs may help us to understand how resistance e both primary and acquired e develops;ultimately allow us to harness the true potential of current therapies.This review will cover the basic structure of the skin,the mutations and pathways responsible for transforming melanocytes into melanomas,the process by which melanomas metastasize,targeted therapeutics,and the potential that noncoding RNAs have as a prognostic and treatment tool.