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With DRE having proven its efficacy in successfully killing this aggressive, chemoresistant form of skin cancer, DRE toxicity on normal cells had to be evaluated

DRE was found to reduce cell viability in a dose-dependent fashion, over time, in A375 melanoma cells as was measured by WST-1 assay. Based on metabolic activity of A375s, it was confirmed that treatment at 2.5 mg/mL DRE resulted in ~50% reduction in cell viability against control within 24 hours (Figure 1(a))

Higher doses were then used and a response was observed at a concentration of 10 mg/mL (

Typical apoptotic morphology was observed in G361 cells treated with DRE starting at 5 mg/mL concentrations for 72 hours

) is more than a worthy chemopreventative, it is fast-acting, nontoxic, and therefore specific in its targeting of human melanoma cancer cells, making it a valuable chemotherapeutic. We have investigated the induction of apoptosis in human malignant melanoma cells and observed its long-term effects in human melanoma cancer.

We are yet to determine the effect of each of the individual components (such as the family of triterpene alcohols and phenolic acids—found in the roots—and cinnamic acids, flavinoids and coumarins—that are found in the leaves

Given that DRE has traditionally been used naturopathically for a variety of ailments, we assume that it would be relatively nontoxic to healthy cells. Our results show that the Normal Human Fibroblasts (NHFs) (which were treated at a low population doubling where NHFs have the best proliferation rate) and Peripheral Blood Mononuclear Cells remained unaffected and healthy after a 96-hour and 48- hour exposure to DRE, respectively (Figures 2(a)–2(d)).

Lupeol,

taraxasterol

More importantly, an increase in ROS production indicates prooxidant behaviour of DRE on cancer cell mitochondria, which is contrary to the antioxidant convictions of traditional medicine and previous studies on Taraxacum extracts citing reductions in NO, ROS, RNS, and COX-2 [10, 11] in mouse macrophages.

There are two main points that must be stated here: firstly, that noncancerous cells are unaffected by DRE treatment, and secondly, melanoma cells retain the signals to commit suicide long after DRE has been removed from the system

By 48 hours, human melanoma A375 cells uncharacteristically showed susceptibility to apoptosis induction by DRE

We believe that this nontoxic extract can undergo precipitous translation from bench top to bedside, with dandelion products that are already commercially available in the form of tea and supplements.

The optimum ALN gel formulation reduced mean relative carcinoma volume (MCV) at a higher rate (p < 0.05) compared with free amygdalin solution and free tamoxifene suspension.

Histological examination of the optimum ALN gel treated group (Figure 7F) showed clearly healed skin with normal covering epithelium and marked improvement in all signs of the epidermis and dermis that were better than those of the oral amygdalin solution. These results confirmed the effectiveness of amygdalin loaded niosomes gel as a cancer therapy in vivo.

Histological examination of the optimum ALN gel-treated group (Figure 8B) showed clearly healed skin with normal covering epithelium.

The group treated with plain niosomes gel showed MCV nearly similar to that of the DMBA control group.

The optimum ALN gel enhanced the permeation of amygdalin into deep skin layers and showed significant anti-tumor activity compared with oral tamoxifen.

which might represent a novel non-toxic alternative to conventional cancer therapy available today.

These results clearly indicate that dandelion root extract can inhibit the ability of colorectal cancer cells to migrate and invade, and therefore metastasize to secondary locations.

morphological differences in tissue slices between the control untreated and the DRE treated group

aken together, these results established that systemic oral intake of the DRE was safe and its anti-cancer efficacy should be further investigated.

, but the DRE treatment efficiently suppressed the growth of both p53 WT and p53 mutant tumors in-vivo (Figure 4B – 4C)

with no difference between the control and DRE treated samples of NCM460

Others suggest that following activation, caspases re-localize to the mitochondria, where they interact with other pro-apoptotic proteins during the progression of apoptosis [15]. A third option, put forward by Qin and colleagues, suggests that inactive caspases are kept in the mitochondria, but following apoptotic stimuli and activation, they are released from the mitochondria into the cytoplasmic peri-nuclear space [

The results showed a progressive destabilization of the mitochondrial membrane following the DRE treatment, which was observed as early as 30 minutes post treatment (Figure ​6C). Pro-caspase-8 (green) was localized in the mitochondria (red) in control untreated cells; however, following the DRE treatment, activated caspase-8 was released from the mitochondria into cytoplasmic space, as indicated by the dispersed green fluorescence (Figure ​6C

suggesting that in HT-29 colorectal cancer cells the DRE-induced cell death was caspase-8 independent.

We observed a decrease in the viability of cells treated with α-amyrin, with 10 μM as the most effective concentration.

However, these results indicate that DRE and its anti-cancer components must be absorbed and circulated, in order to reach the site of the tumor (in order to inhibit tumor growth).

, we confirmed the vulnerability of cancer cell mitochondria by showing that the DRE treatment led to a decrease in the mitochondrial membrane potential and increase in ROS levels in the isolated mitochondria.

caspase-8 specific inhibitor, IETD-fmk, did not change the DRE response in these cells. This was in contrast to our previous study in leukemia and pancreatic cancer cells

he pro-apoptotic genes including Caspase-1, Interferon gamma and the TNF ligands and receptors, were up-regulated in HT-29 cells, prior to the apoptosis induction, while the same genes were down-regulated in NCM460 cells.

Previous findings show that taraxasterol has anti-inflammatory and chemopreventive activit

suggesting its importance in the anti-cancer activity of dandelion root extract, especially on the expression levels of COX-2. Additionally, we show that 10 μM lupeol is not very effective on its own

. EGCG was able to restore the activity of aztreonam against MDR P. aeruginosa . The data presented support further evaluation of the aztreonam–EGCG combination and highlight its potential for use in clinical medici

Polyphenols

Chemicals, media, bacterial isolates and animals

To access synergy between aztreonam and EGCG, checkerboard assays were performed

In conclusion, the results from this study demonstrate that synergy exists between aztreonam and EGCG against MDR clinical strains of P. aeruginosa in vitro and in vivo. EGCG is also able to restore the antibacterial activity of aztreonam to concentrations below the EUCAST susceptibility breakpoint for P. aeruginosa , potentially expanding and extending its useful therapeutic lifespan. Further work should be undertaken to determine if this combination has the potential to treat clinical infections caused by MDR P. aeruginosa .