How Cancer cells get their energy from fermentation?

Koustav Maiti, Ramakrishna Mission Vivekananda Centenary College, Rahara

A normal cell always has the characteristics of regulated cell division, proliferation and lastly undergoes apoptosis (programmed cell death). But when the cell does not have control over its division, it causes a tumor. When the neoplastic cells are clustered together but don’t spread anywhere else within the body, then it is called a Benign tumor (usually harmless). When the neoplastic cells grow without any control and spread in all of the body parts due to metastasis, then it is called a Malignant tumor (Cancer).

German chemist Otto Warburg (In the 1920s) discovered that the cancer cell does not undertake the similar pathway of sugar (generally glucose)  metabolism as the normal cell. But the scientists could not find out the reason why the cancerous cell uses the less efficient pathway.

But now the scientists of the Massachusetts Institute of Technology (MIT) have found the proper explanation of the earlier said statement. This research is conducted by Matthew Vander Heiden (associate professor of Biology at MIT and associate director of MIT’S Koch Institute for Integrative Cancer Research), postdoc Alba Luengo PhD’18 and graduate student Zhaoqi Li.

They showed that the cancerous cells get NAD+ from fermentation to synthesize DNA and other useful molecules. In some conditions, cells need more electron transfer reactions to make DNA which needs more amount of NAD+. There are 2 fates of pyruvate (CH3COCOOH), the end product of glycolysis has 2 fates. Firstly, it can undergo Aerobic respiration in presence of oxygen which can produce more ATP. Otherwise, it can undergo anaerobic respiration and fermentation in the absence or less presence of oxygen. Fermentation does not involve electron transport and ATP is synthesized by Oxidative Phosphorylation. In this process, NAD+ is produced from NADH by transferring electrons and lastly produces Lactate (CH3CHOHCOOH)  and Ethanol (CH3CH2OH) from pyruvate which is the end product of glycolysis. Fermentation is less efficient than respiration as glucose does not break down completely and produce less ATP.

Warburg said that mitochondria (where aerobic respiration takes place) might be damaged. This may the reason to metabolize through the fermentation process. But this is not the case. 

MIT scientists treated the cells with a drug that changes the pathway from fermentation to aerobic respiration. It significantly slows down the growth of the cancerous cell. But when they added a drug that triggers the production of NAD+, they saw that the cell again started to differentiate rapidly though the fermentation was not worked. Then they conclude that NAD+ is more important than ATP for the rapid growth of the cell. ATP is produced much more than NAD+ in the aerobic process. NAD+ production decreases if the cell collects much more ATP than the cell uses. Fermentation will produce more NAD+ to grow quickly.

The scientists also observed it in other cells like immune cells and yeast; they found the same happening. The rapidly growing cells need this process rather than the normal cells. There are 2 ways by which we can treat tumors :

1. The drug which influences to come back to the aerobic respiration pathway instead of fermentation.

2. The drug which can inhibit the production of NAD+ that helps in the rapid growth of the cell.

Also read:Can Bacteria go into Hibernation?

REFERENCE:https://news.mit.edu/2021/cancer-cells-waste-energy-0115

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