Everything Cures Melanoma....#8

Here's links to previous reports:  Everything Cures Melanoma...#7
And I recently reported this:  I like me some shrimp!!! Now their micro-RNA can suppress the stem like qualities of some melanoma cells???!!!

But there's still more...

The Inhibitory Activity of Luzonicosides from the Starfish Echinaster luzonicus against Human Melanoma Cells. Malyarenko, Dyshlovoy, Kicha, et al.  Mar Drugs. 2017 Jul 18.    

Malignant melanoma is the most dangerous form of skin cancer, with a rapidly increasing incidence rate. Despite recent advances in melanoma research following the approval of several novel targeted and immuno-therapies, the majority of oncological patients will ultimately perish from the disease. Thus, new effective drugs are still required. Starfish steroid glycosides possess different biological activities, including antitumor activity. The current study focused on the determination of the in vitro inhibitory activity and the mechanism of action of cyclic steroid glycosides isolated from the starfish Echinaster luzonicus-luzonicoside A (LuzA) and luzonicoside D (LuzD)-in human melanoma RPMI-7951 and SK-Mel-28 cell lines. LuzA inhibited proliferation, the formation of colonies, and the migration of SK-Mel-28 cells significantly more than LuzD. Anti-cancer activity has been ascribed to cell cycle regulation and apoptosis induction. The molecular mechanism of action appears to be related to the regulation of the activity of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), along with Survivin, Bcl-2, p21 and cyclin D1 level. Overall, our findings support a potential anti-cancer efficacy of luzonicosides A and D on human melanoma cells.

Antitumor activity and expression profiles of genes induced by sulforaphane in human melanoma cells. Arcidiacono, Ragonese, Stabile, et al. Eur J Nutr. 2017 Sep 1.  

Human melanoma is a highly aggressive incurable cancer due to intrinsic cellular resistance to apoptosis, reprogramming, proliferation and survival during tumour progression. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, plays a role in carcinogenesis in many cancer types. However, the cytotoxic molecular mechanisms and gene expression profiles promoted by SFN in human melanoma remain unknown.

Three different cell lines were used: two human melanoma A375 and 501MEL and human epidermal melanocytes (HEMa). Cell viability and proliferation, cell cycle analysis, cell migration and invasion and protein expression and phosphorylation status of Akt and p53 upon SFN treatment were determined. RNA-seq of A375 was performed at different time points after SFN treatment.

We demonstrated that SFN strongly decreased cell viability and proliferation, induced G₂/M cell cycle arrest, promoted apoptosis through the activation of caspases 3, 8, 9 and hampered migration and invasion abilities in the melanoma cell lines. Remarkably, HEMa cells were not affected by SFN treatment. Transcriptomic analysis revealed regulation of genes involved in response to stress, apoptosis/cell death and metabolic processes. SFN upregulated the expression of pro-apoptotic genes, such as p53, BAX, PUMA, FAS and MDM2; promoted cell cycle inhibition and growth arrest by upregulating EGR1, GADD45B, ATF3 and CDKN1A; and simultaneously acted as a potent inhibitor of genotoxicity by launching the stress-inducible protein network (HMOX1, HSPA1A, HSPA6, SOD1).

Overall, the data show that SFN cytotoxicity in melanoma derives from complex and concurrent mechanisms during carcinogenesis, which makes it a promising cancer prevention agent.

Anti-Melanogenic Activity and Cytotoxicity of Pistacia vera Hull on Human Melanoma SKMEL-3 Cells. Sarkhail, Salimi, Sarkheil, et al. Acta Med Iran. 2017 Jul. 

Pistacia vera seed is a common food and medicinal seed in Iran. It's hull (outer skin) as a significant byproduct of pistachio, is traditionally used as tonic, sedative and antidiarrheal and has been shown to be a rich source of antioxidants. The aim of the present study is to evaluate the anti-melanogenic activity of the pistachio hulls in order to discover a new alternative herbal agent to treat skin hyperpigmentation disorders. In this work, antioxidant and anti-tyrosinase activity of MeOH extract from Pistacia vera hull (MPH) were evaluated in vitro, respectively, by DPPH radical scavenging and mushroom tyrosinase activity assays. Then the effect of MPH on the melanin content, cellular tyrosinase activity and cytotoxicity (MTT assay) on human melanoma SKMEL-3 cell were determined followed by 72 h incubation. The results indicated that MPH had valuable DPPH radical scavenging effect and weak anti-tyrosinase activity when compared to the well-known antioxidant (BHT) and tyrosinase inhibitor (kojic acid), respectively. MPH, at a high dose (0.5 mg/mL), showed significant cytotoxic activity (~63%) and strong anti-melanogenic effect (~57%) on SKMEL-3 cells. The effect of MPH in the reduction of melanin content may be related to its cytotoxicity. The results obtained suggest that MPH can be used as an effective agent in the treatment of some skin hyperpigmentation disorders such as melanoma.

Molecular characterisation, ontogeny and expression analysis of melanoma differentiation-associated factor 5 (MDA5) from Asian seabass, Lates calcarifer. Paria, Makesh, Chaudhari, et al. Dev Comp Immunol. 2017 Sep 15.    

MDA5 is the pivotal member of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and is reported to play a crucial role in type I IFN-mediated responses against pathogen-associated molecular patterns (PAMPs), especially nucleic acids. In this study, we have identified and cloned the full-length cDNA sequence of MDA5, which comprises 3398 nucleotides and encodes for a putative protein of 978 AA length, in Asian seabass, Lates calcarifer. From the putative amino acid sequence of AsMDA5, four different conserved domains could be predicted: two N-terminal CARD domains, a DExDc domain, a HELICc domain and a C-terminal RIG-1_C-RD domain. The mRNA transcript of AsMDA5 could be detected in all the 11 tissues tested in healthy animals with the highest expression in heart followed by gill and skin. The ontogenetic expression profile showed constitutive expression in developmental stages starting from unfertilized eggs, which implies the possibility of maternally acquired immunity of RLRs in offspring. The viral analogue poly I:C could modulate the AsMDA5 expression both in vivo and in vitro. In all the tissues, AsMDA5 expression was found to be highly regulated following injection with poly I:C with the highest expression observed in kidney. The expression level of AsMDA5 was found to be modulated at different time-points following challenge with Gram-negative bacterium, Vibrio alginolyticus, and Gram-positive bacterium, Staphylococcus aureus. Similarly, noticeable change in AsMDA5 expression was detected in SISK cell line induced with either LPS or PGN. The observations made in this study suggest that in euryhaline marine teleosts like Asian seabass, MDA5 gene serves as one of the pivotal receptor for the detection of viral and bacterial PAMP, and might play an important antimicrobial role during early embryonic development.

Antiproliferative Activity of Walnut (Juglans regia L.) Proteins and Walnut Protein Hydrolysates. Carrillo, Gomez-Ruiz, Ruiz, Carvalho.  J Med Food. 2017 Sep 25.   

Proteins from Juglans regia L. were isolated. Then, proteins were hydrolyzed with different enzymes. Antiproliferative activity of proteins and of the protein hydrolysates of J. regia L. were evaluated using the sulforhodamine B method. Glutelin and prolamin proteins presented a high antiproliferative activity against cancer cells PC-3 (prostate) and K-562 (leukemia) with values of 43.9 and 84.4 μg/mL, respectively. The highest inhibitory effect observed was 50% at 0.25 μg/mL concentration in gastrointestinal digestion with pepsin and corolase pp in a dose-dependent manner against cancer cell UACC62 (melanoma). Pepsin hydrolysate showed inhibitory effects against cancer cell UACC62 (melanoma) with a concentration of 71.0 μg/mL. The effects were studied in a dose-dependent manner. The hydrolysate obtained with neutrase enzyme presented inhibitory effects against cancer cell UACC62 (melanoma) at a concentration of 25 μg/mL. Neither proteins nor protein hydrolysates presented cytotoxicity against normal cell assay VERO (epithelial).

In vitro and in vivo anti-cancer activity of dichloromethane fraction of Triticum aestivum sprouts. Ki, Poudel, Lee, et al.  Biomed Pharmacother. 2017 Sep 29.

Triticum aestivum sprouts (TA) contain significant amounts of chlorophyll, minerals, enzymes, and other functional entities. Furthermore, TA extracts have been shown to possess anti-obesity, anti-diabetic and hepatoprotective effects and are believed to help blood flow, digestion, and general detoxification of the body. In this study, the mechanism underlying the anti-cancer effects of a dichloromethane fraction of TA (TDF) was investigated in vitro and in vivo. In vitro study was done by examining cancer cells growth, morphological changes, cell cycles, expressions of death receptors and apoptosis-linked proteins in wide range of human cancer cell lines. To investigate the effect of TDF in vivo, C57BL/6 mice were injected with B16 melanoma cells and orally administered TDF. TDF markedly inhibited cancer cell growth and induced cellular morphological alterations, cell cycle arrest and apoptosis, and enhanced the expressions of death receptors (DR)-4, 5, and 6 in cell lines. In addition, TDF regulated the expressions mitochondrial apoptosis-linked proteins and induced caspase-dependent cell death. It also significantly enhanced phosphorylation of ERK1/2 and JNK, but not p38, whereas inhibited the activation of NF-κB in cancer cells. In our mouse model, TDF significantly suppressed B16 melanoma growth, to an extent similar to cisplatin (reference control) and augmented immunomodulatory cytokines. In brief, this study presents the mechanism responsible for the anti-cancer effects of TDF in vitro and in vivo.

WOW!! So....to cure our melanoma, we need a little smidge of starfish goo/hormones, cruciferous veggies (Think cabbage, collards, broccoli, brussel sprouts.....stuff I've eaten all my life!!!), the HULL from pistachios  (Just the hull, mind you!!  What do these folks think I am, a termite????), walnut protein (Uh, NO!!  Not for me...as a person with anaphylaxis to tree nuts, I don't think that will turn out very well!!), TA sprouts (That's wheat sprouts, folks!) and my favorite from this list, Asian Sea Bass.    How do you get Asian Sea Bass, you might ask?  Just call them...real loud!!!

Ernie and Bert go Fishing - Sesame Street Rocks!!!  

If any of these work out that will be great!  Til then....I'm just gonna enjoy Bert and Ernie!! - c