While certain things are greater than the sum of their parts, this seems not to be the case with some cancer treatments. Rather than increasing their overall efficacy, combining two anti-inflammatories may, in fact, have the opposite effect. Results from the LBMCC lab actually show diminished anti-cancer activity versus using one of the drugs alone.

The two components of the combination treatment attack cancer cells in different ways—an approach that has had promising results in studies of colon cancer, for example. But, until now, research had only looked at solid tumors. The work of the Luxembourg-based team led by Prof. Marc Diederich is the first to address different types of leukemia, or cancer of the blood-producing tissues.

Fighting Inflammation and Cancer

Chronic inflammation is tied to cancer risk and tumor growth, and anti-inflammatory compounds provide one promising therapeutic approach. Celecoxib, for example, is a synthetic drug effective at blocking the inflammation involved in different cancers. Combining such drugs with other treatments, like radiation therapy, can even have synergistic effects, showing greater success than either had alone.

However, when taken over long periods at the high doses needed to see an effect, drugs like Celecoxib can have serious side effects, like increased risk of heart attack and stroke. (The drug Vioxx, a member of the same family, was taken off the market in 2004 for this reason.) Using Celecoxib at lower doses in combination with another sort of anti-inflammatory, a natural substance that operates by a different mechanism, became an attractive idea for cancer therapy.

Credit: Simon A. Eugster / Wikimedia Commons

Decreased Rate of Cell Death

The source of the second anti-inflammatory used by Prof. Diederich’s team at the LBMCC was the plant that gives us turmeric, the brightly colored spice commonly used in Indian cuisine. Extracted from Curcuma longa, curcumin is used in traditional Chinese and Ayurvedic medicines and acts against tumors’ growth and ability to invade healthy tissue.

Specifically, one thing it seems to do is disrupt the normal cell cycle, the phases a cell passes through from one division to the next. By blocking cancer cells from making the last transition that would lead them to divide, curcumin activates the cell death program, known as apoptosis.

Contrary to what had been seen for colon cancer and other solid tumors, the study by Sobolewski and Cerella of the LBMCC showed that the addition of the second anti-inflammatory, Celecoxib, before or along with curcumin treatment, actually decreased the level of cell death. It seems to have prevented the pile-up of cells at a point in the cycle when curcumin could act on them.

Equipped with this understanding, Prof. Marc Diederich says the team is continuing to target different types of cancer, including leukemias, in such a way as to personalize future treatments. Numerous mechanisms leading to the desired synergy remain to be explored. The LBMCC team at Kirchberg Hospital are moving quickly in this area, in order to better target the molecular characteristics of leukemias and lymphomas, for example. Progress is being made toward tailor-made treatments for patients.

This research, which was supported by grants from Télévie and Action Lions “Vaincre le Cancer”, reveals that, while two individual drugs may show promise for stopping cancer, the effect of using them together must be investigated, or the results could be quite the opposite of those intended.

Original study:

Sobolewski, C., Muller, F., Cerella, C., Dicato, M. and Diederich, M. (2015), Celecoxib prevents curcumin-induced apoptosis in a hematopoietic cancer cell model. Mol. Carcinog., 54: 999–1013. doi: 10.1002/mc.22169

Front page image:

Steven Jackson / Flickr