Mel’s Diner

Melatonin potentiates flavone-induced apoptosis in human colon cancer cells by increasing the level of glycolytic end products.

– Melatonin has been described to possess cell protecting activity in normal cells but was shown to induce apoptotic cell death in cancer cells. It potentiates apoptosis induced by the flavonoid flavone significantly. A combination of flavone and melatonin increased caspase-3-like activity 30-fold and 80% of cells exhibited fragmentation of DNA when compared to untreated controls. Melatonin caused an increase in cytosolic lactate levels that most likely allows the flavone-induced activation of the mitochondrial pyruvate/lactate importer to deliver more substrates to mitochondrial respiration.

Melatonin Enhances the Anti-Tumor Effect of Fisetin

– Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells.

 

linkRoll_2020.04.13

Who Had Their Finger on the Magic of Life – Antoine Bechamp or Louis Pasteur?

PDF | CELLULAR SENESCENCE- AGING, CANCER, AND INJURY

Inducers of Senescence, Toxic Compounds, and Senolytics – We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy.

Cancer, aging and cellular senescence – Normal cells do not divide indefinitely due to a process termed cellular or replicative senescence. Several lines of evidence suggest that replicative senescence evolved to protect higher eukaryotes, particularly mammals, from developing cancer. Senescent cells differ from their pre-senescent counterparts in three way:

  1. They arrest growth and cannot be stimulated to reenter the cell cycle by physiological mitogens;
  2. They become resistant to apoptotic cell death;
  3. They acquire altered differentiated functions.

Replicative senescence occurs because, owing to the biochemistry of DNA replication, cells acquire one or more critically short telomere. The mechanism by which a short telomere induces the senescent phenotype is unknown. Recent findings suggest that certain types of DNA damage and inappropriate mitogenic signals can also cause cells to adopt a senescent phenotype. Thus, cells respond to a number of potentially oncogenic stimuli by adopting a senescent phenotype. These findings suggest that the senescence response is a fail-safe mechanism that protects cells from tumorigenic transformation.

Despite the protection from cancer conveyed by cellular senescence and other mechanisms that suppress tumorigenesis, the development of cancer is almost inevitable as mammalian organisms age. Why is this the case? Certainly, aging predisposes cells to accumulate mutations, several of which are necessary before malignant transformation occurs, particularly in humans. However, many benign or relatively well-controlled tumors may also harbor many potentially oncogenic mutations, suggesting that the tissue microenvironment can suppress the expression of many malignant phenotypes. Although the idea remains controversial, cellular senescence has also been proposed to contribute to organismal aging. Senescent cells have recently been shown to accumulate with age in human tissues. One possibility is that the tissue microenvironment is disrupted by the accumulation of dysfunctional senescent cells. Thus, mutation accumulation may synergize with the accumulation of senescent cells, leading to increasing risk for developing cancer that is a hallmark of mammalian aging.

Cellular Senescence

Metabolic reprogramming and cancer progression

Anticancer Efficacy of Polyphenols and Their Combinations – Polyphenols are classified based on the number of phenol rings and the structural elements that bind these rings to one another. The groups include: phenolic acids, stilbenes, lignans, and flavonoids. Flavonoids, which have both antioxidant and anti-inflammatory properties, are found in fruits, vegetables, legumes, red wine, and green tea. They are subdivided into six classes: flavonols, flavones, isoflavones, flavanones, anthocyanidins, and flavanols (catechins and proanthocyanidins). Flavonols, the most ubiquitous flavonoids in foods, are generally present at relatively low concentrations. Quercetin and kaempferol are the main representatives, and their richest sources are onions, curly kale, leeks, broccoli, and blueberries.

Anti-androgenic effects of flavonols in prostate cancer – GOOD READ

Efflux (microbiology) – All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that are transcribed and translated to efflux pumps. Efflux pumps are capable of moving a variety of different toxic compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters via active efflux, which is vital part for xenobiotic metabolism. Efflux pumps are proteinaceous transporters localized in the cytoplasmic membrane of all kinds of cells. They are active transporters, meaning that they require a source of chemical energy to perform their function.

Magic Beans – Lysine and Proline

L-Proline & L-Lysine supplement
L-Proline & L-Lysine supplement label

How it Works, from www.cancertutor.com

The Dr. Rath Cellular Solution is theorized to stop the spreading (i.e. metastasis) of cancer via stopping the destruction of the collagen matrix by enzymes secreted by cancerous cells, thus stopping the cancer from spreading. If the cancer is contained the body can usually deal with the cancer.

The Dr. Rath Cellular Solution

This quote explains how Dr. Rath felt cancer cells spread:

Cancer cells produce and secrete millions of enzyme molecules, which, like scissors [cancer scissors], cut collagen and tissue that surrounds cells. This picture shows how liver cancer cells use these enzymes to cut little holes in the blood vessel wall and get into the blood stream where they can travel to other organs, such as the lungs. Using the same mechanism, cancer cells can settle and start new tumor growth.

~Dr. Aleksandra Niedzwiecki, Rath Foundation

This quote explains more things about the importance of the connective tissue:

Connective tissue functions not only as a mechanical support for other tissues but also as an avenue for communication and transport among other tissues. Most significantly, connective tissue is the stage for inflammation. The principal cell types involved in immunological defense are found within connective tissue.

The Dr. Rath Cellular Solution consists of two amino acids, L-Lysine and L-Proline, plus Vitamin C, and a substance in Green Tea, the polyphenol catechin known as epigallocatechin gallate (EGCG). Laboratory trials and human trials have suggested the effectiveness of this combination.

It should be noted that Dr. Rath worked with two-time Nobel Prize winning chemist Linus Pauling on a heart disease prevention program. The three key elements of the heart prevention program are the same elements in the cancer solution (excluding the EGCG).


Additional Reading

Polyphenolic Profile and Biological Activity of Chinese Hawthorn (Crataegus pinnatifida BUNGE) Fruits

 

Fighting Fisetin

What an incredibly tool in the hands of a skilled craftsman. The following is my unwieldy rack of tabs. As of April 07, 2020.


Sensing seriousness about senolytics

www.fightaging.comFisetin – Animal data shows fisetin to be a surprisingly effective senolytic

Forever Healthy Knowledge Base

Fisetin Senolytic Therapy

Anticancer Efficacy of Polyphenols and Their Combinations

Blocking negative effects of senescence in human skin fibroblasts with a plant extracts