Is diabetes medication the cure for cancer?

The CDC estimates that in 2014 29.1 million people had diabetes, with 8.2 million people living without a diagnosis of their condition. One of the most popular medications to help those with diabetes is Metformin. One popular brand name of metformin is Glucophage, although it is marketed as part of a variety of diabetes medications. It is an oral medication given to diabetics and people that are pre-diabetic in order to help control glucose levels and increase insulin sensitivity. Some studies in the past have found diabetes medications can also help with other problems, such as preventing cardiovascular disease and polycystic ovary syndrome. While interesting these studies have limited impact on treatment options besides diabetes.

New studies, like the one linked below, are starting to test and see if metformin can help to treat cancer and decrease tumor growth. It has long been known that controlling glucose levels in diabetics is key to lower the incidence of other diseases, even some that at first do not seem related to glucose levels. The exact mechanism of metformin is unknown, and the extent of biochemical pathways it interacts with has been increased as more research has been done. This has been researched since the 1950s and things are still being discovered about the mechanisms of action exhibited in the body. One thing that has been found is that metformin activates the AMPK pathway, leading to increased glucose uptake in cells.

The AMPK pathway has also been linked antineoplastic properties, since the AMPK pathway will upregulate mRNA that degrades a long noncoding RNA called H19. H19 serves to stop methylation of some genes by inactivating an enzyme called SAHH. With H19 knocked down by the addition of metformin, SAHH will help a methyltransferase methylate many oncogenes, leading to decreased growth in cancer cells. It is hypothesized that this reaction will also serve to keep healthy cells from becoming cancerous as well.

Since metformin is near side effect free it is safe for use by people without diabetes and is much less destructive than many current cancer treatments. Hopefully, after further testing and better elucidation of all of the pathways metformin interacts with, metformin can be used to create better cancer treatments. 

Want to see articles? Check it out below:

Metformin alters DNA methylation genome wide via the H10/SAHHH axis

By: T. Zhong, Y. men, L. Lu, et al. http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016391a.html

Cellular and molecular mechanisms of metformin: an overview

By: B Viollet, B Guigas

Diabetes Stats:

http://www.cdc.gov/diabetes/data/statistics/2014statisticsreport.html

 

Miracle Berries and how we can use them

There is a particularly unique plant in west Africa that I find interesting. The Synsepalum dulcificum is a plant that grows a berry containing the aptly named glycoprotein call miraculin. When consumed miraculin makes sour foods taste sweet. While eating the berry this effect can last from thirty minutes to an hour.  The actually name miracle fruit or miracle berry can be used to describe a few different plants, but all the plants share the same characteristic of altering the perception of taste.

While the exact mechanism of miraculin is unknown it is known that it binds to taste receptors on the tongue. When miraculin is exposed to lower pH, which is typical for acidic sour foods, it will change the binding to the taste receptors, activating the sweet receptors, causing any sour foods to seem sweet. Miracle berries are safe to eat and have been consumed in west Africa for some time without any reported side effects. The properties of miraculin have led to it being tested as a food additive. The only minor drawback is that miraculin can be denatured by heat, however it is still being tested and in some places used to sweeten diet sodas.

It has not been approved in the U.S., however with no negative outcomes being linked to consumption and with additional benefits coming to light that may be subject to change. Recent studies have tested miraculin as a supplement to control uric acid, a category known as anti-hyperuricaemia agents. High uric acid levels can cause gout and kidney stones. These problems occur more often among overweight populations, and finding a way to control uric acid levels could be beneficial to many people with chronic uric acid related problems. In the study I linked below miraculin lowered uric acid levels in mice as effectively as allopurinol, a commonly used drug for gout sufferers. The name miracle berry was given long before these benefits were known, however with these new benefits coming to life it makes the name even more appropriate.

The use of natural subsatnces to make modern medical treatments is a common occurrence. Many medicines have similar origin stories. Let me know what you think in the comments below.

For more reading on how miraculin decreases uric acid levels: 

Miracle Fruit (Synsepalum dulcificum) Exhibits as a Novel Anti-Hyperuricaemia Agent

Authors: Yeu-Ching Shi

Molecules. 2016, Vol. 21 Issue 2, p1-13.

ISSN: 1420-3049

DOI: 10.3390/molecules21020140

Autophagy: The Newest Nobel Prize

The newest Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi for his work on understanding and elucidating the mechanisms of autophagy. He has a doctorate of science from the University of Tokyo and has had professorships at multiple colleges in Japan. Much of his work has been on the vacuole of simple yeast. His decades of research have led to wide ranging advances in the understanding of autophagy and its relation to bodily processes. He also characterized many of the genes that code for the proteins involved in autophagy, as well as some mutations of the same genes.

Autophagy is the mechanism by which cells degrade and reuse cellular components that are no longer necessary. It involves the sequestration, transport, degradation, and recycling of material.  The body recycles components through the use of lysosomes, one part of the autophagy process. Autophagy is an important part of many biochemical processes and has been linked to many different causes and outcomes in cells from a variety of species. There are three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy is commonly triggered in response to physical stresses on the body, that forces it to efficiently clean and reuse cell materials. Some of these physical stresses include starvation and disease.

The degradation caused by autophagy helps power the cell in these trying times and it can also protect against infection and viruses. It has a role in a multitude of disease responses and can cause programmed cell death. Having said that there are many diseases that occur because of malfunctions in the autophagy process. When the mechanism malfunctions because of mutations in the genes that code for proteins involved in the process there has been linked to osteoarthritis, cancer, and Parkinson disease.

I highly recommend reading the interview of Yoshinori Ohsumi that I linked below. He talks about how he followed his interests to continue his research and at the end he shares some advice to younger scientists.

For more reading:

An interesting interview of Professor Ohsumi where he talks about the progression of his work:

Yoshinori Ohsumi: Autophagy from beginning to end

By: Caitlin Sedwick

J Cell Biol. 2012 Apr 16; 197(2): 164–165

http://jcb.rupress.org/content/197/2/164

Some more in depth information on autophagy:

Autophagy: process and function

By: Noboru Mizushima

http://genesdev.cshlp.org/content/21/22/2861.long

Developments in HIV Research

As a little introduction to the topic I will explain how Human Immunodeficiency Virus (HIV) works. HIV is a retrovirus, meaning that it infects cells and uses reverse transcriptase to infect normal cells with the genetic material of the virus. HIV creates RNA then uses a reverse transcriptase protein to integrate a complimentary DNA strand into the DNA of the host cell. HIV is particularly deadly because it attacks macrophages, dendritic cells, and CD4 helper T-cells, an integral part of the immune system. It can be spread through the transfer of many bodily fluids such as blood, semen, breast milk, or vaginal secretions. The virus has a long incubation period and is also known as a lentivirus. It infects CD4 cells, using them to replicate and over time it lowers the amount of CD4 cells in the blood to levels too low to stop infections. People with the lowest CD4 count are diagnosed as having stage 4 HIV infection, often called AIDS, or Acquired Immune Deficiency Syndrome.  

HIV is a relatively new disease, only being discovered in 1983. There is not a cure widely available and most treatments are a combination of drugs designed to limit the viral load in fluids to undetectable levels, which reduces transmission rates and increases the life span. If treatment is stopped the virus will begin replicating back to pre-treatment levels. Only one man has been cured of HIV, by being giving a bone marrow transplant from someone with natural immunity to the disease. It was a rare circumstance that cannot be replicated readily since bone marrow transplants are expensive and matches are hard to find, particularly since immunity to HIV is rare.  A few days ago a new series of treatments also produced a patient with no viral load, although further observation is needed to if this was a permanent solution.  

This research paper focuses on some of the inner workings of the cells that have been infected by HIV. It was thought that when a cell was infected with HIV it did not realize it was infected and the cell did not attempt to fight the infection. In reality this paper shows that the cells recognize HIV replication products and produce type 1 interferon. This would normally fight off many types of infections, however HIV produces accessory proteins that regulate interferon production. In many cases interferon is ineffective at fighting HIV and causes inflammation that is detrimental to the patient.  

Finding new things about HIV infections opens up new avenues of research. This research could lead to effective cures that work quicker and cheaper than those being researched now. It also shows that the understanding of this disease is not complete. What do you think about this ongoing research? Do you think HIV will be effectively cured sometime in the future?  

For more reading on research about HIV here is the journal article I started on:  

HIV Triggers a cGAS-Dependent, Vpu- and Vpr- Regulated Type I Interferon Response in CD4+ T Cells 

By: Jolien Vermeire, Bruno Verhasselt, et. al