So....just to keep y'all up to date on the latest and greatest, I keep reporting all things (well...almost all....some things are just too far fetched to make even THIS list!!!) peeps are looking at to "Cure" melanoma. Here's a link to the last installment: Everything Cures Melanoma!!! (And yes, we're up to installment #9 - with no actual cure!)
Now, there's this.....
Chrysin, a natural and biologically active flavonoid suppresses tumor growth of mouse B16F10 melanoma cells: In vitro and In vivo study. Sassi, Maatouk, El Gueder, et al. Chem Biol Interact. 2018 Jan 15.
Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound which has many biological activities as an anticancer agent. The current report is aimed at finding out whether the antitumor potential of chrysin, evidenced in vitro and in vivo, is linked or not to its effect on immunological mechanisms of melanoma-bearing mice. Chrysin-treated B16F10 cells were analyzed for their metabolic rate and apoptotic potentials. In vivo, BALB/c mice received a subcutaneous injection of B16F10 melanoma cells prior to antitumor treatments with chrysin (50 mg/kg b.w) for 14 days and 21 days. The results showed that chrysin inhibited cancer cell growth at a dose-dependent manner by inducing apoptosis and cell cycle arrest at G2/M phase. Moreover, chrysin suppressed melanoma tumor growth at an average of 60% (after 14 days of treatment) and 71% (after 21 days of treatment) compared to the tumor-bearing group. Furthermore, chrysin treatment increased the cytotoxic activity of NK, CTL and macrophages. The findings showed that chrysin antitumor action on the murine melanoma model was very promising, suggesting that chrysin could be a potentially good candidate for future use in alternative anti-melanoma treatments.
So, at least in 70% of poor little mice given melanoma, chrysin, found in honey and most often extracted from blue passion flowers, melanoma tumor growth was suppressed after about a month of treatment.
Oridonin inhibits migration, invasion, adhesion and TGF-β1-induced epithelial-mesenchymal transition of melanoma cells by inhibiting the activity of PI3K/Akt/GSK-3β signaling pathway. Li, Wang, Shen, et al. Oncol Lett. 2018 Jan;15.
Epithelial-mesenchymal transition (EMT) has been reported to play pivotal roles in tumor invasion and metastasis. Inhibition of EMT may exert beneficial effects in regulating metastasis. Oridonin (ORI), an active diterpenoid compound isolated from Rabdosia rubescens, was found to be a potent anti-metastatic agent. However, the possible involvement of ORI in the EMT in malignant melanoma is unclear. The present study found that ORI inhibited cell migration, invasion, and adhesion in A375 and B16-F10 melanoma cells. The transforming growth factor-β1 (TGF-β1)-induced EMT was also inhibited in ORI-treated cells, as reflected in the upregulation of E-cadherin, and downregulation of vimentin and Snail. Similar results were observed in A375 and B16-F10 melanoma cells treated with ORI. Furthermore, pre-treatment with ORI blocked the TGF-β1-induced phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (Akt)/glycogen synthase kinase (GSK)-3β signaling pathway activation. These effects mimicked PI3 kinase inhibitor LY294002 treatment. ORI interfered with the PI3K/Akt/GSK-3β pathway, and reversed TGF-β1-induced EMT, which suppressed the invasion and metastasis of melanoma cells. Taken together, the present study demonstrated that ORI inhibits melanoma cells migration, invasion, and adhesion and TGF-β1-induced EMT through the PI3K/Akt/GSK-3β signaling pathway. These findings suggest that ORI is a promising anti-metastasis agent for melanoma.
In this study, oridonin (ORI) extracted from a herb (the isodon plant) kept melanoma cells in a petri dish from getting their groove on!!! Apparently it has had various uses in Japan, China, and Korea as a herbal remedy and was examined here as well: Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on leukemia in vitro and in vivo. Blood Journal, 2007.
Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice. Kokolus, Zhang, Sivik, et al. Oncoimmunology. 2017 Dec 21.
Immunotherapy has expanded treatment options for cancers with historically poor outcomes, yet a significant proportion of patients still fail to achieve durable clinical benefit. We defined the contribution of β-adrenergic receptor (βAR) signaling, a component of the stress response, on success of immunotherapy for melanoma since the use of antagonists (β-blockers) is associated with improved clinical outcomes in some cancers. We show that metastatic melanoma patients who received immunotherapy had improved overall survival if they also received pan β-blockers. This retrospective analysis is reinforced by results showing that βAR blockade enhances the control of murine melanoma growth by anti-(α)PD-1 checkpoint blockade. However, this effect was most significant when β-blocker was combined with dual αPD-1 + high dose interleukin-2 therapy and was reproduced by selective blockade of β2ARs. These results identify a novel strategy that can be quickly introduced to potentially increase the number of patients who benefit from immune-based therapies.
I first reported on Propranolol use in melanoma back in 2014 here: Kill melanoma....with snake venom or Vietnamese sophora root...beta-blockers...not so much! Where it was noted that: "Beta-blockers were prescribed after malignant melanoma diagnosis to 20.2% of 242 patients who died from malignant melanoma and 20.3% of 886 matched controls. Contrary to some previous studies, beta-blocker usage after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in the UK population based study." In the report above, researchers state that they saw improved OS in melanoma peeps who were simultaneously given immunotherapy, as was the case for more poor little melanoma affected mice. They do point out that the effect was greater when melanoma peeps (or maybe they mean the mice...it's not clear) were also given high dose IL-2 with their anti-PD-1/beta blocker cocktail!
Antioxidative and Anti-Melanogenic Activities of Bamboo Stems (Phyllostachys nigra variety henosis) via PKA/CREB-Mediated MITF Downregulation in B16F10 Melanoma Cells. Choi, Jo, Yang, et al. Int J Mol Sci. 2018 Jan 30.
Phyllostachys nigra var. henosis, a domestic bamboo species, has been attracting much attention; its bioactive compounds (especially in the leaf) show antioxidant, anti-inflammatory, and anti-obesity activities. Little information is available on the antioxidative and anti-melanogenetic activities of the bioactive compounds in bamboo stems. The anti-melanogenic and antioxidative activities of the EtOAc fraction (PN3) of a P. nigra stem extract were investigated in a cell-free system and in B16F10 melanoma cells. PN3 consisted of a mixture of flavonoids, such as catechin, chlorogenic acid, caffeic acid, and p-coumaric acid. The antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)), and hydroxyl radical scavenging) was evaluated, as well as the inhibition of reactive oxygen species (ROS) produced by the Fenton reaction. PN3 showed in vitro tyrosinase inhibition activity with the half maximal inbihitory concentration (IC50) values of 240 μg/mL, and in vivo cytotoxic concentration ranges > 100 μg/mL. The protein expression levels and mRNA transcription levels of TYR, TRP-1, and MITF were decreased in a dose-dependent manner by the treatment with PN3. PN3 interfered with the phosphorylation of intracellular protein kinase A (PKA)/cAMP response element-binding protein (CREB), demonstrating potent anti-melanogenic effects. PN3 could inhibit PKA/CREB and the subsequent degradation of microphthalmia-associated transcription factor (MITF), resulting in the suppression of melanogenic enzymes and melanin production, probably because of the presence of flavonoid compounds. These properties make it a candidate as an additive to whitening cosmetics.
|RK1, the first very short peptide
from Buthus occitanus tunetanus inhibits tumor cell migration,
proliferation and angiogenesis. Kjammessi, Ben Mabrouk, El
Fessi-Magouri, Krarrat. Biochem Biophys Res Commun. 2018
Scorpion toxins have been the subject of many studies which explore their pharmacological potential toward diverse molecular targets, known to monitor key mechanisms in cancer such as proliferation, migration and angiogenesis. The few peptides from scorpion venom that have an anti-tumor effect are generally cytotoxic. Herein, we present the first description of a short 14 amino acid peptide (called RK1), purified from the venom of Buthus occitanus tunetanus, with the particular capabilities, among different other scorpion peptides, to inhibit cell proliferation, migration and angiogenesis of U87 (Glioblastoma) and IGR39 (Melanoma). Moreover, RK1 is a first peptide derived from scorpion venom exhibiting a potential anti-tumoral activity with no manifest toxicity. Our results suggest that, in terms of its primary structure, RK1 is unique compared to a variety of known peptides purified from scorpion venoms. In addition, RK1 is the first natural peptide able to abolish completely the proliferation of cancer cells. The Chicken chorioallantoic membrane model revealed that RK1 strongly inhibits ex-vivo vascular growth. RK1 could open new perspective for the pharmaceutical application of short scorpion venom peptides in anticancer activity and may represent the first member of a new group of scorpion peptides
Propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR/p70S6K signaling pathway in melanoma cells. Shang, Feng, Cuj, et al. Oncol Lett. 2018 Jan;15.
Propofol is an intravenous anesthetic, which is widely used in clinical anesthesia induction and maintenance and is critical in the sedation of patients. However, the functions and mechanisms of propofol on apoptosis of melanoma cells remain unclear. The present study investigated whether propofol promotes cell apoptosis and suppresses the HOX transcript antisense RNA (HOTAIR)-mediated mechanistic target of rapamycin (mTOR) pathway in melanoma cells. B16F10 cells were cultured with different concentrations (0-10 µM) of propofol for 24 or 48 h. Proliferation and apoptosis of B16F10 cells were detected using MTT assay and flow cytometry. The pcDNA 3.1(-)-HOTAIR and pcDNA 3.1(-)-control plasmids were transfected into B16F10 cells using Lipofectamine 2000. In the present study, treatment with propofol significantly reduced viability, and induced apoptosis and caspase-3 activity in melanoma cells. Propofol treatment significantly inhibited HOTAIR expression and the expression of phosphorylated (p)-mTOR and p- p70S6K protein in melanoma cells. Overexpression of HOTAIR significantly increased viability of melanoma cells, and increased HOTAIR, p-mTOR and p-p70S6K protein expression in melanoma cells. These results indicated that propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR signaling pathway in melanoma cells.
In this study, once again, in the petri dish, melanoma cells couldn't get their groove on when treated with proprofol. That's good! Of course, the rest of the body can't get its groove on either if one is given too much propofol!!!!
|Thai Water Lily Extract Induces
B16 Melanoma Cell Apoptosis and Inhibits Cellular Invasion Through
the Role of Cellular Oxidants. Aimvijarn, Palipoch, Okada,
Suwannalert. Asian Pac J Cancer Prev. 2018 Jan 27.
Melanoma is a cancer that is associated with a high capacity of invasion. Oxidative stress is recognized as cancer growth and progression. The phytochemical pigments of natural products show either anti-oxidant or pro-oxidant activity from the redox system. In addition, the phytophenolics also prevent cancer cell proliferation and progression. This study aims to investigate the effects of Thai water lily on cell apoptosis and cellular invasion through the role of cellular oxidants in B16 melanoma cells. The cytotoxicity and cell apoptosis of Thai water lily extract treating B16 cells were performed by using the MTT and Annexin V/PI-flow cytometry methods, respectively. In addition, cellular oxidants and cancer cell invasion were also obtained by using DCFH-DA and Boyden chamber assays, respectively. Thai water lily, Nymphaea stellate extract was shown to be markedly toxic to B16 melanoma cells with IC50 = 814 μg/ml. The extract at 800 and 1,000 μg/ml demonstrated pro-oxidant activity relating to the cell apoptosis. The low concentrations of the extract at 200 and 400 μg/ml showed the anti-oxidant function associated with the inhibitory effect of melanoma cell invasion. Thai water lily extract may play an important role in bioactive work as a chemo preventive agent on the modulation of cellular oxidative stress-induced apoptosis and suppressed cancer cell invasion.
Lectin Isolated from Japanese Red Sword Beans (Canavalia gladiata) as a Potential Cancer Chemopreventive Agent. Une, Nonaka, and Akiyama. J Food Sci. 2018 Feb.
So, this is a bummer. For all the good things that curcumin (derived from mustard seeds) is supposed to do for melanoma peeps...we now have to worry if the mustard seeds used were grown in selenium rich soil!! GAH!!!!!
Helix aspersa maxima mucus exhibits antimelanogenic and antitumoral effects against melanoma cells. Ellijimi, Ben Hammouda, Othman, et al. Biomed Pharmacother. 2018 May.
Wow!!! Snail slime??? Really??? Well, if it works, okay!!! Hope we won't have to eat it!!!
Hang in there, my melanoma peeps!! Thanks to all the researchers (esp the ones who had to deal with snail slime!!!), petri dishes and melanoma mice! Maybe something wonderful is in the offing!!! - c