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New Evidence Backs Up Warburg Cancer Theory

https://www.medicalnewstoday.com/mnt/releases/135271#1

Primary Category: Oncology and Cancer

Biochemistry and biology are also covered.

Date of Article: January 13, 2009, 7:00 PDT

Otto H. Warburg, a German scientist, won the Nobel Prize in 1931 for his idea regarding the causes of cancer, but the molecular underpinnings of his theory remained obscure.

Eventually, his notion that cancer develops from irreparable damage to cellular respiration was disproved by research that implicated genetic mutations as the root of unchecked cell growth.

Researchers from Boston College and Washington University School of Medicine have reported new evidence in favor of the original Warburg Theory of Cancer, which was awarded the highest scientific distinction seventy-eight years after Warburg got it.

Warburg, a pioneering biochemist and a descendant of German aristocracy, first hypothesized in 1924 that the primary cause of cancer was damage to a cell brought on by impairment to a cell’s power plant, or energy metabolism, located in its mitochondria.

Tumor and cancer cells produce energy through the non-oxidative breakdown of glucose, a process known as glycolysis, in contrast to healthy cells, which do so through the oxidative breakdown of a simple acid inside the mitochondria. Glycolysis is, in fact, the metabolic signature of the majority, if not all, cancer forms. Warburg stated that since healthy cells and cancer cells differ from one another, cancer should be seen as a form of a mitochondrial disease.

As researchers discovered instead that genetic abnormalities within cells triggered malignant transformation and unregulated cell development, Warburg’s idea sparked controversy and debate in the years that followed. Since no mitochondrial anomalies could be uncovered that were consistently linked to malignant transformation in malignancies, several experts concluded that Warburg’s discoveries actually highlighted the symptoms of cancer rather than its causes.

By analyzing mitochondrial lipids in a variety of mouse brain tumors, particularly a complex lipid known as cardiolipin, Boston College biologists and associates at Washington University School of Medicine discovered further proof in favor of Warburg’s idea (CL). Their research was published in the Journal of Lipid Research’s December issue.

Cardiolipin abnormalities can hinder the mitochondria’s ability to produce energy. Michael Kiebish, a doctoral candidate at Boston College, Professors Thomas N. Seyfried and Jeffrey Chuang compared the levels of cardiolipin in healthy mouse brain mitochondria with the levels of CL in several mouse brain tumor specimens. To examine the lipid properties of the samples of normal and malignant mitochondria, bioinformatic models were used. All forms of malignancies exhibited significant alterations in the content or composition of cardiolipin, which were strongly related to notable reductions in energy-generating activities.

The results were in line with cardiolipin’s critical function in preserving the structural integrity of a cell’s inner mitochondrial membrane, which is in charge of generating energy. The co-authors write that the findings “may link mitochondrial lipid deficiencies to the Warburg theory of cancer and suggest that cardiolipin abnormalities can underlie the permanent respiratory injury in malignancies.”

These findings can help scientists develop new cancer treatments that don’t harm healthy cells while taking advantage of the bioenergetic flaws in malignant cells.

Co-authors Xianlin Han and Hua Cheng from the Department of Internal Medicine at Washington University School of Medicine in St. Louis joined Seyfried, Chuang, and Kiebish.

Edward Hayward,

Boston University