Antioxidant Suppression Decimates Pancreatic Cancer Cells

3-list-antioxidants-foodNew research at Cold Spring Harbor Laboratory (CSHL) in New York has revealed that a novel drug therapy that mimics the suppression of an antioxidant-promoting protein kills pancreatic cancer cells.

Pancreatic cancer is caused by the abnormal, uncontrolled growth of cells in the pancreas.

The team  found that reducing levels of antioxidants in pancreatic cells can help to kill them. This novel strategy for wiping out pancreatic cancer cells may open new doors for treating this serious illness, in which less than 5% percent of patients survive beyond 5 years.

Antioxidant” is currently a popular buzzword that is viewed as a panacea for health ailments; it is widely believed that raising levels of antioxidants stops cancer cells from developing.

The reality is that although antioxidants interact with and neutralise free radicals and prevent them from causing damage, there is minimal evidence that antioxidants actually prevent cancer.

Does increasing antioxidant levels do more harm than good?

CSHL researchers demonstrated, in a series of complex experiments, that in pancreatic cells that are abnormal or in a malignant state, raising antioxidant levels can actually do more harm than good.

The amounts of oxidising and anti-oxidising agents in healthy cells, are kept precisely balanced in every cell. In proliferating cancer cells that are increasing rapidly in number through growth and cell division however, the amounts of oxidants in malignant cells increase, but anti-oxidants also increase to counter the impact of rising oxidation.

CSHL’s Prof. David Tuveson – M.D., Ph.D., director of research for the Lustgarten Foundation – and colleagues note that without the amounts of antioxidants going up in scale with the oxidants, malignant cells will die from excessive oxidation.

Of course, that’s exactly what we want cancer cells to do – to burn themselves out,” says Iok In Christine Chio, a postdoctoral investigator in the Tuveson lab who led the experiments.

The therapeutic principle our lab is testing is whether, by increasing the level of oxidation in cancer cells, we can cause pre-malignant and malignant cells to die,” she adds.

Excessive oxidation causes cells to commit suicide

Treatments for cancer such as radiation therapy and chemotherapy destroy cancer cells by promoting oxidation. Although antioxidants protect cellular DNA from damage by oxidative stress, they in all probability protect cancer cells as well.

Exposing cells to excessive oxidation causes them to experience programmed cell death called apoptosis. A method of increasing oxidation in cancer cells is to decrease levels of antioxidants within the same cells.

Tuveson and team aimed to find a technique whereby they could increase oxidation without harming healthy cells. They concentrated on NRF2, a protein that can be tweaked to disrupt the balance between oxidation and decreased cancer cells.

When NRF2 is active, cells synthesise a chemical called glutathione, an important antioxidant. However, it is not possible to reduce NRF2 activity or make it inactive, as it has a role in regulating several hundred different genes.

One can’t delete it from a cell without impacting many other processes,” says Chio.

The team used samples of pancreas cells from people with pancreatic cancer (malignant and pre-malignant) and individuals with a healthy pancreas to conduct an experiment where NRF2 was eliminated.

Normal pancreas cells not harmed by two-drug treatment

They found that when NRF2 was missing, the process of translating messages from the genes into proteins was highly affected by the oxidant and antioxidant balance, but only in the cancerous cells. The healthy cells were still able to produce the proteins.

We were very excited when we saw this. This meant that if we could find a way of reducing antioxidants, protein synthesis would only be impacted in precancerous and malignant cells, a potentially powerful therapeutic strategy.” Iok In Christine Chio, postdoctoral investigator, Tuveson Lab

The crux of the experiment was to use two drugs in combination: an AKT (protein kinase B) inhibitor, and a BSO (buthionine sulfoximine), which reduces levels of glutathione.

AKT inhibitors have been used in trials on cancer patients before but with limited success. The team wanted to combine this with the BSO to mimic what would happen if they could reduce levels of NRF2.

We were able to test this idea and see that this approach was synthetically lethal – it did increase the killing power of the AKT inhibitor, but the synergy was not present in the setting of normal pancreas cells,” Chio says. Fundamentally, healthy pancreas cells were not damaged by the treatment.

The team hopes their findings can enable them to propose new treatments and approaches for cancer patients, and they hope to start clinical trials in the near future.



About LFCT

This is a blog about CHILDHOOD CANCER and CHILDHOOD CANCER AWARENESS Little Fighters Cancer Trust is a non-profit organisation that offers support and aid to Children with Cancer and their families. When a child is diagnosed with cancer it affects the whole family. One of the parents, usually the mother, must give up their job to care for the child and this creates financial problems for the family. In South Africa especially the majority of these families are not well-to-do; many of them are rural. A diagnosis of cancer can wipe out any family’s finances, let alone a poor family. The costs of special medications, special diets, hospital stays, transport to and from the hospital or clinic and accommodation and food costs for the mother who spends most of the time at her child’s bedside are astronomical. These are the people and problems that fall through the cracks, and these are the people that Little Fighters Cancer Trust has pledged to help in any way possible. LFCT takes a holistic approach to assisting the Children with Cancer and their Families, with the main aim to be the preservation of individual dignity and pride. Little Fighters Cancer Trust also focuses on promotion and advocacy of National Childhood Cancer Awareness in an effort to increase awareness of Early Warning Signs of Childhood Cancer. This would result in earlier diagnosis, giving the Child with Cancer more of a chance at Treatment and Survival. See "About" for more Background info

Posted on 18 August, 2016, in Alternative Treatments, Blog, Research. Bookmark the permalink. Leave a comment.

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