Over-the-counter decongestant found to be effective inhibitor of tumor stroma

In continuation of my update on N-Acetyl cysteine  - or NAC

CANCER researchers seeking non-toxic alternatives to harmful chemotherapy are reporting a highly significant result for a humble cold remedy.

N-Acetyl cysteine  - or NAC - is routinely used as a dietary supplement and as a decongestant given to children to ward off a cold.

Now, clinical trials in the US indicate the cheap, over-the-counter drug, is a first rate inhibitor of the tumor stroma, a cell compartment which is fundamental to the spread of cancer.

The results, published in Seminars in Oncology, confirm a long-held theory that cancer cells are being sustained and strengthened by the presence of MCT4, a protein which 'brings them' energy, in the form of lactate, from neighboring cells.

Patients taking high dosages of NAC saw their levels of the 'transporter' protein fall by more than 80%, drastically reducing the ability of the cancer cells to feed off neighboring cells.

Professor Federica Sotgia, of the Biomedical Research Centre at the University of Salford, UK, explained: "In cell cultures in the laboratory, we had seen a near complete reduction in MCT4, but to achieve such a substantial result in breast cancer patients is extremely exciting indeed."

The team, which includes Professor Michael Lisanti, of the University of Salford and US-based Ubaldo Martinez-Outschoorn, MD, conducted a 'window trial' on 12 patients awaiting surgery for breast cancer at The Sidney Kimmel Cancer Center (Thomas Jefferson University), in Philadelphia.

Patients were given maximum daily dosages of the over-the-counter drug for three weeks between diagnosis and surgery. Tumor tissue biopsies were then taken before and during surgery and key biomarkers, including MCT4 and K167, were measured post-surgery.

K167 levels fell by 25% and MCT4 levels were reduced by approximately 80%.

"High levels of stromal MCT4 are extremely worrying, as they are linked to aggressive cancer behavior and poor overall survival, so this is very encouraging result," explained Professor Lisanti.

"Our idea was to repurpose an inexpensive FDA-approved drug, to examine if its antioxidant properties could target the feeding behavior of cancer cells.  To be able to inhibit MCT4 protein expression, in a non-toxic way, is huge step forward."

Over-the-counter decongestant found to be effective inhibitor of tumor stroma

Natural molecule NAC could benefit patients with Parkinson's disease

The natural molecule, n-acetylcysteine (NAC), with strong antioxidant effects, shows potential benefit as part of the management for patients with Parkinson's disease, according to a study published today in the journal PLOS ONE. Combining clinical evaluations of a patient's mental and physical abilities with brain imaging studies that tracked the levels of dopamine, the lack of which is thought to cause Parkinson's, doctors from the Departments of Integrative Medicine, Neurology, and Radiology, at Thomas Jefferson University showed that patients receiving NAC improved on both measures.

 Acetylcysteine

Current treatments for Parkinson's disease are generally limited to temporarily replacing dopamine in the brain as well as some medications designed to slow the progression of the disease process. Recently, researchers have shown that oxidative stress in the brain may play a critical role in the Parkinson's disease process, and that this stress also lowers levels of glutathione, a chemical produced by the brain to counteract oxidative stress. Studies in brain cells showed that NAC helps reduce oxidative damage to neurons by helping restore the levels of the antioxidant glutathione. NAC is an oral supplement that can be obtained at most nutrition stores, and interestingly also comes in an intravenous form which is used to protect the liver in acetaminophen overdose.

"This study reveals a potentially new avenue for managing Parkinson's patients and shows that n-acetylcysteine may have a unique physiological effect that alters the disease process and enables dopamine neurons to recover some function," said senior author on the paper Daniel Monti, M.D., M.B.A., Director of the Myrna Brind Center of Integrative Medicine, and the Brind-Marcus Center of Integrative Medicine at Thomas Jefferson University.

In this study, Parkinson's patients who continued their current standard of care treatment, were placed into two groups. The first group received a combination of oral and intravenous (IV) NAC for three months. These patients received 50mg/kg NAC intravenously once per week and 600mg NAC orally 2x per day on the non IV days. The second group, the control patients, received only their standard of care for Parkinson's treatment. Patients were evaluated initially, before starting the NAC and then after three months of receiving the NAC while the control patients were simply evaluated initially and three months later. The evaluation consisted of standard clinical measures such as the Unified Parkinson's Disease Rating Scale (UPDRS), a survey administered by doctors to help determine the stage of disease, and a brain scan via DaTscan SPECT imaging, which measures the amount of dopamine transporter in the basal ganglia, the area most affected by the Parkinson's disease process. Compared to controls, the patients receiving NAC had improvements of 4-9 percent in dopamine transporter binding and also had improvements in their UPDRS score of about 13 percent.

"We have not previously seen an intervention for Parkinson's disease have this kind of effect on the brain," said first author and neuro-imaging expert Andrew Newberg, M.D., Professor at the Sidney Kimmel Medical College at Jefferson and Director of Research at the Myrna Brind Center of Integrative Medicine. The investigators hope that this research will open up new avenues of treatment for Parkinson's disease patients.

S-methylmethionine (Vitamin U) as antiulcer agent .......

About S-methylthionine :

S-Methylmethionine, or S-methyl-L-methionine, is a derivative of methionine In plants, it is produced from methionine by the enzyme methionine S-methyltransferase. S-Methyl- methionine is sometimes called vitamin U in naturopathic medicine, but it is not recognized as a vitamin by mainstream nutrition science. Methionine in itself has not been demonstrated as effective for treating peptic and duodenal ulcers. Its proponents claim that sources of methionine are limited, or claim it can be found only in raw cabbage; however, these claims are incorrect. Methionine is a common amino acid found in a wide variety of fruits, vegetables, and legumes.

More interesting results by the researchers from the Stanford University, have further substantiated the claim that it can be used to treat peptic and duodenal ulcers.

Acetaminophen is a pain reliever present in many over-the-counter cold and flu medicines. It is broken down, or metabolized, in the body into byproducts , one of which can be very toxic to the liver. At normal, therapeutic levels, this byproduct is easily deactivated when it binds to a naturally occurring, protective molecule called glutathione. But the body's glutathione stores are finite, and are quickly depleted when the recommended doses of acetaminophen are exceeded. Acetaminophen overdose is the most common cause of liver transplantation and the only effective antidote is an unpalatable compound called NAC that can induce nausea and vomiting, and must be administered as soon as possible after the overdose.

As per the claim by the authors, an enzyme called Bhmt2 helped to generate more glutathione. Bhmt2 works by converting the diet-derived molecule S-methylmethionine, or SMM, into methionine, which is subsequently converted in a series of steps into glutathione. The researchers confirmed the importance of the pathway by showing that SMM conferred protection against acetaminophen-induced liver toxicity only in strains of mice in which the Bhmt2 pathway was functional.

By administering SMM, which is found in every flowering plant and vegetable, we were able to prevent a lot of the drug’s toxic effect,” said Peltz. He and his colleagues are now working to set up clinical trials at Stanford to see whether it will have a similar effect in humans. In the meantime, though, he cautions against assuming that dosing oneself with SMM will protect against acetaminophen overdose....

Source : http://med.stanford.edu/ism/2009/november/peltz.html