Antimalarial drug, paired with light-sensitive molecules, is promising cancer treatment

Sept. 26, 2017
The combination could kill colorectal cancer cells and suppress tumor growth more effectively than administering artemisinin alone.

Scientists from the National University of Singapore (NUS) have demonstrated that the anti-cancer properties of artemisinin, a potent anti-malarial drug, could be enhanced tenfold when used in combination with aminolaevulinic acid (ALA), a photosensitizer that, upon exposure to light, leads to generation of free radicals that can kill cells. ALA is used in photodynamic therapy, in combination with a special light source, to treat various types of cancer, including skin and prostate cancer.

Related: Near-IR photodynamic therapy approach effectively targets prostate cancer

A team led by Lin Qingsong from the Department of Biological Sciences at NUS Faculty of Science, together with Wang Jigang and Shen Han-Ming from the Department of Physiology at NUS Yong Loo Lin School of Medicine, discovered that a combination of artemisinin and ALA could kill colorectal cancer cells and suppress tumor growth more effectively than administering artemisinin alone.

NUS scientists Lin Qingsong (left) and Wang Jigang (right) discovered that a combination of artemisinin, which is a potent anti-malarial drug, and aminolaevulinic acid, which is a photosensitizer, could kill colorectal cancer cells and suppress tumor growth more effectively than administering artemisinin alone. This novel combination therapy could also have fewer side effects.

"Artemisinin has been reported to possess anti-cancer activities in recent years, but the mechanism of the drug has not been well understood," Lin explains. "In this study, we found that the anti-cancer mechanism of artemisinin resembles its action towards malaria parasites."

The research team had previously conducted a study on the antimalarial mechanism of artemisinin and its potent parasite-killing effect. The study showed that artemisinin is activated by haem, an iron-containing compound that is an essential component of many biologically important proteins such as hemoglobin and many metabolic pathway enzymes. Malaria parasites rely on hemoglobin as their food when they reside in red blood cells. Digestion of hemoglobin by the parasites releases large amount of haem, leading to activation of artemisinin in the parasites, attacking multiple proteins that are essential for their survival and thus killing them.

In the new study, the researchers found that cancer cells have higher haem levels compared to the non-cancer cells, and an elevated haem biosynthesis pathway. This is likely because cancer cells have higher rates of metabolism, and many metabolic pathway enzymes require haem for their activities. Upon activation by haem in cancer cells, artemisinin attacks more than 300 proteins, many of which are important for the survival of cancer cells.

Guided by this mechanism, the team also discovered that the anti-cancer activity of artemisinin can be further enhanced with addition of ALA, a clinically used haem synthesis precursor, to increase haem levels inside the cancer cells. The researchers found that ALA co-treatment significantly enhanced the killing effect of artemisinin against colorectal cancer cells, whereas the drug combination has minimal effect on the non-cancer cells.

"Having developed a better understanding of the anti-cancer activity of artemisinin in colorectal cancer, we will also be testing this combination treatment on other cancer types, such as liver cancer," Shen says.

Full details of the work appear in the journal ACS Central Science.

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