Monday, July 17, 2017

Everything Cures Melanoma....# 7

Yep, the list of melanoma cures (in a petri dish - for the most part) is long and varied!!!  The short list includes ~ coffee (multiple reports), tea, doxycycline, curcumin and curry (many reports), cimetadine, NSAID's, shiitake mushrooms, exercise, red wine, strawberry juice, snake venom, sephora root, glycoalkaloids (found in eggplants, potatoes, and tomatoes), dill and parsley extracts, wild olive leaves, emu oil, oyster extract, Brazilian lima beans, lichen, sandalwood, beta blockers, and vitamin D (there may actually be something to this one!!) ~ to name a few!!!  Here are links to the data:  Everything Cures Melanoma: Installment #6

But, there is still more!

Melanoma and brown seaweed: an integrative hypothesis.  Teas, Irhimeh.  J Apppl Phycol. 2017.  

Although relatively rare, melanoma accounts for 2 % of cancer diagnoses globally and accounts for about 1 % of all cancer deaths. Worldwide, the annual incidence of melanoma is 272,000 cases which vary hugely, ranging from Japan where it is incredibly infrequent, to Queensland, Australia, where it is nearly 100 times higher. Based on epidemiology and laboratory studies, there is compelling evidence suggesting that seaweed might be protective against different types of cancers such as breast cancer in seaweed consuming populations. By comparing countries where melanoma is more common with countries where it is infrequent, it is possible to construct a hypothesis for how consuming brown seaweeds which may hold clues to the differences in melanoma susceptibility between Japanese and Western nations. Unlike in these other countries, where melanoma incidence has increased dramatically over the last two decades, in Japan, rates have remained remarkably low and stable. There is limited evidence from clinical studies and animal models that have used whole seaweed or isolated fractions from seaweed and measured changes in biomarkers. They have demonstrated the effectiveness of seaweed at inhibiting melanoma development and progression. In this review, the various results will be described. Although there are several effective fractions, it is proposed that consuming whole seaweeds may hold additional benefits that could be lost by consuming only a single extract.
Mitochondria-Associated Apoptosis in Human Melanoma Cells Induced by Cardanol Monoene from Cashew Nut Shell Liquid. Su, Lin, Yu, et al. J Agric Food Chem. 2017 Jun 19.  

Cardanol monoene (CM) is the major phenolic component extracted from cashew nut shell liquid (CNSL), which has been relevant to wide range of biological effects. In this study, we found that CM could inhibit the M14 human melanoma cells proliferation in a dose dependent and time dependent manner, and the IC50 values were determined to be 23.15 ± 2.42 μM and 12.30 ± 1.67 μM after 24 h and 48 h treatment, respectively. The flow cytometric analysis demonstrated that CM induced M14 cell cycle arrest at S phase, along with the collapse of mitochondrial membrane potential (ΔΨm) and the accumulation of reactive oxygen species (ROS) level in cells but the apoptotic cells reduced when treated with Z-VAD-FMK (pan-caspase inhibitor). Western blotting showed that the expressions of p53, cytochrome C, caspase-3 and PARP were up-regulated, the expression level of Bax/Bcl-2 ratio increased significantly. The 2527 significant differentially expressed genes were obtained by RNA-seq, which were assigned to 270 KEGG pathways. These results indicated that CM induced M14 cells apoptosis via the ROS triggered mitochondrial-associated pathways, which supports the potential application of CM for the therapy of melanoma cancer.

Young leaves of reed (Phragmites communis) suppress melanogenesis and oxidative stress in B16F10 melanoma cells. Sim, Ham, Lee. Biomed Pharmacother. 2017 Jun 16. 

This study investigated the effects young leaves of reed (Phragmites communis) water extract (YLR) on melanogenesis and oxidative stress using B16F10 cells. YLR decreased the intracellular melanin content, protein expression and enzyme activity of tyrosinase in a dose-dependent manner. YLR significantly decreased the gene and protein expression of melanogeneis-related proteins, such as microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein-1 and -2. In addition, YLR up-regulated the melanogenesis inhibitory proteins, extracellular signal-regulated kinase (ERK) and protein kinase B (AKT), while it dose-dependently down-regulated p38 and cAMP response element-binding protein (CREB). Moreover, YLR significantly reduced H2O2-induced reactive oxygen species levels in B16F10 cells and showed antioxidant activity based on DPPH and ABTS free radical scavenging activity and SOD-like activity. These results suggest that YLR have anti-melanogensis properties that function through regulation of the CREB/MITF/tyrosinase pathway in B16F10 cells and antioxidant activity. Overall, these findings indicate that YLR has the potential for use in treatment of skin disorders and skin-whitening.

A polymethoxyflavone mixture extracted from orange peels, mainly containing nobiletin, 3,3',4',5,6,7,8-heptamethoxyflavone and tangeretin, suppresses melanogenesis through the acidification of cell organelles, including melanosomes. Yoshizaki, Hashizume, Masaki.  J Dermatol Sci. 2017 Jun 10.

Skin color is determined by melanin contents and its distribution. Melanin is synthesized in melanosomes of melanocytes, catalyzed by tyrosinase, melanogenic enzymes. Regarding the process of melanin synthesis, melanosomal pH is considered to play an important role, because it has been reported to differ between Caucasian and Black melanocytes.
Although polymethoxyflavone (PMF) has many beneficial effects, it has not been reported which PMF suppresses melanogenesis. In this study, we identified the mechanism underlying the effect of PMF on melanogenesis METHODS: We determined the effects of a PMF mixture extracted from orange peels on melanogenesis, on tyrosinase expression, on the localization of tyrosinase and on the acidification of organelles, including melanosomes, in HM3KO human melanoma cells. RESULTS TREATMENT: with the PMF mixture elicited the suppression of melanogenesis, the degradation of tyrosinase in lysosomes and the mislocalization of tyrosinase associated with the acidification of intracellular organelles, including melanosomes. The neutralization of cell organelle pH by ammonium chloride restored melanogenesis and the correct localization of tyrosinase to melanosomes, which had been suppressed by the PMF mixture.  These results suggest that the PMF mixture suppresses the localization of tyrosinase to melanosomes and consequently inhibits melanogenesis due to the acidification of cell organelles, including melanosomes.

Bioactivities of ethanol extract from the Antarctic freshwater microalga, Chloromonas sp. Suh, Yang, Lee, et al. Int J Med Sci. 2017 Apr 28.  

Cancer is the principal cause of human death and occurs through highly complex processes that involve the multiple coordinated mechanisms of tumorigenesis. A number of studies have indicated that the microalgae extracts showed anticancer activity in a variety of human cancer cells and can provide a new insight in the development of novel anti-cancer therapy. Here, in order to investigate molecular mechanisms of anticancer activity in the Antarctic freshwater microalga, Chloromonas sp., we prepared ethanol extract of Chloromonas sp. (ETCH) and performed several in vitro assays using human normal keratinocyte (HaCaT) and different types of cancer cells including cervical, melanoma, and breast cancer cells (HeLa, A375 and Hs578T, respectively). We revealed that ETCH had the antioxidant capacity, and caused significant cell growth inhibition and apoptosis of cancer cells in a dose-dependent manner, whereas it showed no anti-proliferation to normal cells. In addition, ETCH had a significant inhibitory effect on cell invasion without the cytotoxic effect. Furthermore, ETCH-induced apoptosis was mediated by increase in pro-apoptotic proteins including cleaved caspase-3 and p53, and by decrease in anti-apoptotic protein, Bcl-2 in ETCH-treated cancer cells. Taken together, this work firstly explored the antioxidant and anticancer activities of an Antarctic freshwater microalga, and ETCH could be a potential therapeutic candidate in the treatment of human cancer.

Anti-Metastatic Effect of Semi-Purified Nuphar Lutea Leaf Extracts. Ozer, Fishman, Eilam, et al.  J Cancer. 2017 May 12.  

Nuphar lutea L. SM., leaf and rhizome extracts (NUP), contain nupharidines as active components. Nupharidines belong to the sesquiterpene lactones class of a naturally occurring plant terpenoids. This family of compounds has gained considerable interest for treating infection, inflammation and cancer. NF-κB is a central, downstream regulator of inflammation, cell proliferation and apoptosis. In our previous work we demonstrated strong inhibition of NF-κB activity and induction of apoptosis by NUP. In addition, NUP exhibited anti-inflammatory properties and partial protection from LPS-induced septic shock by modulating ERK pathway and cytokine secretion in macrophages. In the present study, we examined the effect of NUP in a B16 melanoma experimental murine lung metastasis model and its ability to affect the ERK and NF-κB pathways in variety of cell lines. We showed that NUP and cisplatin combined treatment was synergistic and reduced the lung metastatic load. In addition NUP treatment inhibited TNFα-induced IκBα degradation and NF- κB nuclear translocation. We also observed that NUP induced ERK activation. Furthermore, ERK inhibition prevented NF-κB inactivation by NUP. Overall, our work implies that co-administration of NF-κB inhibitors such as NUP, with standard anti-cancer drugs, may act as "sensitizers" for more effective chemotherapy.

Antiproliferative and proapoptotic activities of anthocyanin and anthocyanidin extracts from blueberry fruits on B16-F10 melanoma cells. Wang, Liu, XU, Liu.Food Nutr Res. 2017 Jun 19.  
Background: Anthocyanins have been proven to affect multiple cancer-associated processes in different cancer cell lines. However, relatively few studies have investigated the effects of blueberry anthocyanins on metastatic melanoma. Thus, this study focuses on evaluating the chemopreventive potential of blueberry anthocyanins and their aglycones (anthocyanidins) in B16-F10 melanoma cells. Methods: Blueberry anthocyanin and anthocyanidin extracts were prepared mainly by combined chromatography techniques. Their antiproliferative and proapoptotic effects on B16-F10 cells were evaluated by MTT assay, calcein acetoxymethyl ester/propidium iodide (calcein-AM/PI) staining, and flow cytometry of the cell cycle and apoptosis. Results: The MTT and calcein-AM/PI staining results showed that both anthocyanin (purity of 62.5%) and anthocyanidin (75.1%) extracts could significantly inhibit the viability and proliferation of B16-F10 cells in a dose-dependent manner, while anthocyanidin extracts exhibited significantly higher (p < 0.05) cytotoxicity than anthocyanin extracts. Furthermore, anthocyanin and anthocyanidin extracts blocked cell cycle procession at the G0/G1 phase below 400 and 200 μg/mL, and induced early apoptosis below 400 and 300 μg/mL, respectively. Conclusions: These data suggest that both anthocyanin and anthocyanidin extracts inhibit the proliferation and trigger the apoptosis of B16-F10 cells, and anthocyanidin extracts may be a more promising candidate in preventing metastatic melanoma than anthocyanin extracts.

Hmmm, brown seaweed, cashew nut SHELL liquid, leaves of young (NOT old!!!) reeds, orange peels, microalga (Is there macro-algae????) from fresh water in the Antartic, lutea leaves, and blueberries!!!  Sounds like yuppie compost!  Hey, whatever works!

For what it's worth! - c

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