PUBLISHED PAPER 2: GLYCOLYSIS AND CANCER

H Pelicano, D S Martin, R-H Xu and P Huang BIBLIOGRAPHY: “Glycolysis inhibition for anti-cancer treatment” Nature, 2006. http://www.nature.com/onc/journal/v25/n34/full/1209597a.html

Hey friends! Today I will be reviewing a scientific paper written on the link between glycolysis and cancer. This paper titled ‘Glycolysis inhibition for anti-cancer treatment’ focused on several enzymes of glycolysis such as: Hexokinase, glycose-6-phosphate isomerase, phosphofructokinase, aldolase, glyceraldehydes-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, Enolase, pyruvate kinase, lactate dehydrogenase as well as several sub-topics which were: the increase of aerobic glycolysis in cancer, mitochondrial respiration injury, hypoxia, the inhibition of glycolysis for anticancer treatment, and the combination of glycolytic inhibition and other anticancer agents. This paper was very long and consisted of great detail in each of the enzymes as well as the above subtopics mentioned. My aim is to summarize the paper as well as comment on what I learnt and how well I understood what I read.

The article spoke about the link between the glycolytic pathway and cancer. The Warburg effect is said to be when the cancer cells show increased glycolysis because they rely on ATP from the glycolytic pathway for energy.  This is one of the most fundamental metabolic alterations and leads to mitochondrial defects and abnormality in the glycolytic enzymes. What scientists have realized was that because these cancer cells were dependent on glycolysis for energy, they can kill the cancer cells by disrupting this dependence. Glycolytic inhibitors are an example that is used to kill cancer cells with these mitochondrial defects and hypoxic conditions.

The article mentioned that preferentially killing cancer cells is one of the greatest considerations in cancer chemotherapy. For effective anticancer drugs and activity, one must first understand the difference between a normal and a cancer cell. What the journal article focused on was the use of the glycolytic pathway to kill cancer cells. The glycolytic pathway is made up of ten stages which is split up into the energy investment and the energy generation phase. Under aerobic conditions pyruvate can be converted to lactic acid by the enzyme lactate dehydrogenase and under aerobic conditions pyruvate can be oxidized to carbon dioxide and water in the mitochondria through the citric acid cycle producing large quantities of ATP.

Reading on further, the article went into great detail about the enzymes present in each stage of the glycolytic pathways and whether they played a significant role in cancer or not. I learnt that Hexokinase is a great target for anticancer agents; glucose-6-phosphate isomerase is associated with aggressive malignant behaviors. Neither phosphofructokinase nor glyceraldehydes-3-phosphate dehydrogenase have any defined role in cancer. Aldolase is found in elevated amounts in individuals with tumors.

The article went on to discuss the increase in aerobic glycolysis in cancer. This phenomenon was first described by Otto Warburg in 1930 when he compared the glycolytic activity of normal and malignant cells.There was great focus on these mechanisms as it was noted that mitochondrial respiration injury is suspected to be responsible for increased glycolysis in cancer cells and hypoxia modulates energy metabolism.

This article was a bit too detailed; however, I was able to understand it and learn about the Warburg effect, which enzymes of the glycolytic pathway are responsible for tumors or aggressive malignancy in cancer cells as well as what was the real link between the glycolytic pathway and these cancer cells. I learnt about the mechanisms and what they were and read about a few experiments that were carried out on this same topic.  I did a bit of my own research after reading the article to ensure that I understood everything and that came out to be very handy in the long run. When studying glycolysis in class I had no idea that it would have any link to cancer and it was very cool to learn about this.

In conclusion, it was obvious to me that cancer cells show a greater amount of aerobic glycolysis in oppose to normal cells as a result of several metabolic changes that causes this dependency on the glycolytic pathway for energy. It was also very interesting to know that by disrupting the glycolytic pathway and the enzymes possibly responsible for cancer mechanisms that we can kill cancer cells. Well guys I hope you found this as interesting as I did! Thanks for reading!

References:

Features Image: http://www.skepticalraptor.com/skepticalraptorblog.php/cancer-treatment-centers-america-advertising/

http://www.nature.com/onc/journal/v25/n34/full/1209597a.html

http://biology.about.com/od/cellularprocesses/a/aa082704a.htm

http://www.cellsignal.com/reference/pathway/warburg_effect.html

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