The Anti-malaria Drug “Artemisinin” Blocks PAK, Being Potentially Useful for Cancer Therapy.

This year Tu YoYo, a Chinese female scientist in Beijing (born in 1930), won the Lasker (Clinical Medicine) Award for her pioneering work to develop a natural compound called “Artemisinin” as an effective anti-malaria drug useful for the treatment of multi-drug resistant malaria strains. Her project, initially coined “523", began on May 23, 1967, towards the end of Mao’s Cultural Revolution, and several years later her team found in a Chinese traditional medicine called “Qinghao” (Artemisia annua L., or sweet wormwood) this new anti-malaria compound.

Interestingly, this year Christian Doerig’s group in Switzerland found that like AIDS virus and H. pylori (bacteria causing stomach ulcer and cancer) , malaria requires the oncogenic kinase PAK1 for its infection (1). In other words some of currently used anti-malaria drugs could cure malaria by blocking PAK1. Yes, Artemisinin happens to be among these PAK1-blocking anti-malaria drugs. Back to 2007, a group at Chinese Academy of Sciences in Shanghai found that this drug inactivates both the G protein RAS and the kinase RAF in T cells (2), clearly indicating that PAK1 is blocked by this drug, because RAS and RAF work just upstream and downstream of PAK1, respectively.

As previously mentioned, more than 70% of cancers in particular solid tumors such as pancreatic and colon cancers, require PAK1 for their growth. In other words, Artemisinin and other PAK-blocking anti-malaria drugs would be potentially useful for the therapy of these PAK1-dependent tumors as well. Yes, in 2010, a Chinese group at Guangdong Medical College clearly demonstrated that a water-soluble derivative of Artemisinin called “Artesunate” (100 mg/kg, i.p., daily) completely blocks the growth of human pancreatic cancer xenografts in mice without any side effect (3).


References:

1. Sicard, A., Semblat, JP., Doerig, C., Hamelin, R. et al. Activation of PAK-MEK
signaling pathway in Malaria parasite-infected erythrocytes. Cell Microbiol. 2011, 13,
836-45.

2. Wang, JX., Tang, W., Shi, LP., Wan, J. et al. Investigation of the immunosuppressive
activity of artemether on T-cell activation and proliferation. Brit. J. Pharmacol. 2007,
150, 652-61.

3. . Du, JH., Zhang, HD., Ma, ZJ., Ji, KM. Artesunate induces oncosis-like cell death in
vitro and has anti-tumor activity against pancratic cancer xenografts in vivo.
Cancer Chemother. Pharmacol. 2010, 65, 895-902.