NewG Lab Pharma

Who is

Otto Heinrich Warburg 1883 ~ 1970

German physiologist. He graduated from the University of Berlin and Heidelberg. Professor at the University of Berlin, and Research director at the Kaiser Wilhelm Physiology Research Center(1931~1970)
Warburg investigated the metabolism of tumors and the respiration of cells, particularly cancer cells, and in 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme"

“Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.”

: Cancer should be interpreted as a mitochondrial dysfunction. - Otto H. Warburg

Cancer is a Metabolic Disease.

The “Warburg effect” is an important content that describes the metabolic
processes of cancer cells that are different from normal cells.

The human body uses a basic energy source called ATP (adenosine triphosphate)
to do physical activity. These ATP are substances that are decomposed through
metabolic processes by ingesting carbohydrates, fats, etc.

The reason we need oxygen is to generate ATP. Normal cells produce 95% of
ATP via metabolic processes called mitochondrial oxidative phosphorylation.
The remaining 5% is made through a phosphate-creatine systems (ATP-PCr system)
or Glycolysis that produces a lot of lactic acid.

Cancer cells, on the other hand, produce more than 50% of the ATP needed through
Glycolysis. Despite the presence of oxygen, using the Glycolysis to produce a large
amount of ATP, it is the Warburg effect discovered by Dr. Warburg in 1924.

Dr. Warburg claimed that the mitochondrial strain is the cause of the Warburg effect,
which causes cancer.

Prof. Peter L. Pedersen

1After Dr. Warburg, Since theories seeking the causes for cancer from
gene variation has been mainstream of cancer research, the theory of
cancer metabolism has been pushed into a fringe group

2In 1960, there were researchers who were interested in the study of
Warburg again. One of the leading scholars is Peter L. Pedersen,
a disciple of the great biochemist Albert Lehninger Ph.D. He has been
researching the cellular energy metabolism process at the Johns Hopkins
University Medical School from 1968 to present.

3Pedersen’s research team have identified several mechanisms of
action in the metabolic processes of cancer.

4In particular, they identified that Hexokinase 2 (HK2) plays an
important role in Warburg Effect, and HK2 has a very close
relationship with the VDAC protein (Voltage Dependent Anion Channel)
in the mitochondrial outer membrane.

Difference between Normal and Cancer
Cell Energy Metabolism

The following figure shows the energy metabolism of normal cells and cancer cells.
While normal cells create 95% of the total ATP using oxygen in the mitochondria, like the picture in the lower right, cancer cells create about 60 percent of
ATP through the Glycolysis, which creates a large amount of lactic acid.

Key Discoveries about

Cancer Cell Metabolism

The following figure is a flowchart showing the metabolic processes of Glycolysis.
From the first stage, Hexokinase is involved as an enzyme where the glucose is changed to
Lactate through Pyruvate. HK2 also Has a Close Association with a protein, Named “VDAC”,
in the Outer Mitochondrial membrane. (VDAC = Voltage Dependent Anion Channel)

Ref : Nakashima, Mangan, Colombini, and Pedersen Biochemistry, 1986
HK2 prevents apoptosis of cancer cells by disturbing the VDAC reacting with Bax, Bad, BCL-XL, etc.
It makes the cancer cells immortal, unlike normal cells.

The following figure shows a Super Complex with a VDAC associated with ATP Synthasome, which produces ATP in the mitochondria.
For cancer cells, you can see that the HK2 is combined in close contact with the VDAC.

Normal Mitochondria
Cancer Mitochondria

HK2 blocks VDAC's normal function for triggering apoptosis.

Key Discoveries about

Cancer Cell Metabolism
The following is a recap of the role of HK2 in cancer cells:

1. Decreases the product inhibition by G-6-P.

2. Increases the access to substrate, ATP.

3. Generates large amounts of G-6-P, a precursor for all cell building blocks.

4. Suppresses apoptosis facilitating cell immortalization.

5. Suppresses the inflammation.

This is why we are concerned about the treatment of cancer targeted at HK2.

About Us

Core Technology

Products

R&D

PR Center

NEWGLAB Core Technology

About Cancer

Otto Heinrich Warburg 1883 ~ 1970

Normal Mitochondria

Cancer Mitochondria