Cancer cells are weaker when made more acidic

Cancer cells function less well and are less able to multiply when their internal environment is made more acidic.

This was the conclusion that researchers in the United States and Spain came to after they used a computer model to study the conditions that affect metabolic pathways in cancer cells.

The model showed that cancer cells need an internal environment that is more alkaline than that of healthy cells for their metabolism to function properly.

It also helped identify some enzymes that work with the more alkaline environment to promote cancer.

The findings could lead to new cancer drugs that target these molecules, according to a paper now published in the journal Nature Communications.

"This work is still very academic," explains study co-author Miquel Duran-Frigola, a computational chemist at the Institute for Research in Biomedicine in Barcelona, Spain, "but we believe that some of the targets identified are ready to be tested in animals, thus allowing us to move into more advanced preclinical trial stages."

Systems biology

The study is an example of the type of research that is going on in the field of systems biology, which uses complex computer models and big data to help us understand the "organizational principles of life."

The researchers brought together a large amount of biochemical and genetic data to develop a molecular model of cancer cell metabolism.

They used the model to explore the response of "almost 2,000 metabolic enzymes" to changes in the internal pH of the cell.

The pH scale is a measure of acidity. An acidic environment has a low pH and an alkaline, or basic, environment has a high pH. A pH of 7 is neutral — it is neither acid nor alkaline.

Healthy cells have a slightly alkaline internal environment with a pH of around 7.2. Cancer cells are more alkaline and have an internal pH that is higher than 7.2.

"By reconstructing and integrating enzymatic pH-dependent activity profiles into cell-specific genome-scale metabolic models," note the authors, "we develop a computational methodology that explores how intracellular pH [...] can modulate metabolism."

Promising results

Using the computer model, the team showed that when its insides remain in the favored alkaline pH zone, the cancer cell is able to proliferate. This condition also favors other functions that the cell relies on, such as "glycolysis and adaptation to hypoxia."

But a lower, more acidic pH in the cancer cell "disables these adaptations and compromises tumor cell growth," note the authors.

The team also used the model to identify metabolic targets that showed "predicted amplified anticancer effects" when the cancer cell's internal environment became more acidic.

Some of the targets have already shown promising results in tests using real breast cancer cells.

"Understanding the link between metabolic pathways that work better under different pHs can give us an idea about the mechanisms used by cancer to survive at basic pH."

Miquel Duran-Frigola