Why high cholesterol can help cancer spread: Mouse study sheds light

  • A study in Petri dishes and mice has investigated the link between high cholesterol levels and cancer cell growth and spread.
  • The analysis suggests that high cholesterol levels fuel cancer cells by increasing resistance to a form of cell death.
  • The discovery indicates that lowering cholesterol levels is not only beneficial for good health but may also become beneficial in the therapeutic regimen for cancer treatment.

Cholesterol — which is a fat-like, waxy substance produced in the liver — aids the production of hormones and essential vitamins in the body.

In large quantities, cholesterol builds up in the body to form deposits known as plaques, which block blood vessels. This may result in a heart attack, a stroke, or another related health problem.

Some research implicates high cholesterol levels in some cancers, but scientists do not fully understand the exact mechanism.

However, scientists at the Duke University School of Medicine in Durham, NC, have recently proposed an explanation for this phenomenon.

By studying cholesterol regulation in cancer cells and mice, they suggest that high cholesterol levels may fuel cancer resistance to cell death, which can worsen disease outcomes.

Their findings reveal a previously undiscovered mechanism through which elevated cholesterol levels influence cancer cells in the body.

Lead scientist Dr. Donald McDonnell, Ph.D. — a professor of pharmacology and cancer biology — explained to Medical News Today the significance of their results.

He said, “We believe [our work] addresses long standing questions regarding the impact of overnutrition, obesity, and dyslipidemia/hypercholesterolemia on cancer pathobiology.”

“There is an abundance of epidemiological evidence linking hypercholesterolemia to poorer outcomes in [people] with most cancers, [and now] we think we have found why and have defined a completely new way to treat these cancers.”

– Dr. Donald McDonnell, Ph.D.

Dr. Lynne Elmore, Ph.D. — senior scientific director of cell biology and preclinical cancer research at the American Cancer Society — also shared this conclusion.

Dr. Elmore explained, “Published data have demonstrated that high cholesterol promotes the growth of estrogen-positive breast and gynecological cancers owing to derivatives of cholesterol that act like estrogen, fueling cancer growth.”

“But in this study,” she added, “the research team observed that cancers that don’t rely on estrogen for growth (estrogen-negative) are still associated with a worse disease by high cholesterol. This strongly suggests that there is at least one other mechanism of cancer action for high cholesterol, which formed the basis for this comprehensive study.”

The results of this study appear in the journal Nature Communications.

High cholesterol levels and immunity from cell death

The researchers carried out their studies using cell lines and mice models.

The results show that 27HC, which is a derivative of cholesterol obtained through oxidation, is implicated in cancers.

In animal models, the researchers observed that chronic exposure to 27HC resulted in the growth of tumors that were highly metastatic — that is, they spread from where they initially formed to other parts of the body.

In an interesting twist, the scientists also discovered that 27HC induced metabolic stress in cancer cells, which allowed them to escape a natural cell death process called ferroptosis. As a result, this increased the tumor-forming ability and metastatic capacity of the cancer cells.

These findings suggest an explanation for the role of cholesterol in cancer cell resistance to cell death, thereby fueling cancer growth and spread.

Dr. Elmore revealed to MNT the importance of understanding what makes cancer cells grow and spread. “If we know the key mediators [of cancer], that could pave the way for developing targeted therapies to treat and perhaps prevent cancers,” she explained.

Promising results

The results from the initial experiments seem promising. However, it is too early to confirm the clinical implications of this study.

For one, Dr. McDonnell and team admit that they have not yet figured out how resistance to ferroptosis increases the tumor-forming ability and metastatic capacity of cancer cells.

They also reveal plans to extend their research to other types of cancers outside of breast and gynecological cancers.

Nevertheless, one thing is clear: The results of this study add to existing information available on cholesterol and cancer. It also goes a step further by exploring other mechanisms of action of cholesterol in cancer, and this may one day have significant clinical importance.

Source: Read Full Article