Beta-Elemene : a herbal PAK1-blocker that up-regulates PAK1-interacting protein 1

  According to a recent paper by a Chinese group, beta-elemene from Curcuma increases the radio-sensitivity of cancer cells by blocking the oncogenic/ageing kinase PAK1 (1).  Both radiation and UV irradiation are known to activate PAK1, making cancer cells more resistant to any anti-cancer drugs. 

How does beta-elemene block PAK1?  They found that it up-regulates a PAK1-inhibitor called "PAK1-interacting protein 1" which binds the N-terminal 70 amino acid motif of PAK1 (2).  

Unfortunately, however, the IC50 of beta-elemene against cancer cells in cell culture is rather high, around 300 micro M. Thus, it is unlikely that be-elemene is clinically useful for cancer therapy.  Thus, another Chinese group developed a far more potent "dimethylpiperazine"  derivative beta-elemenecalled IIi whose IC50 against cancer cells in cell culture is around 3 micro M (3).

  
References:

1。Liu JS¹, Che XM¹, Chang S¹, Qiu GL¹, He SC¹, Fan L¹, Zhao W¹, Zhang ZL¹, Wang SF¹ β-elemene enhances the radiosensitivity of gastric cancer cells by inhibiting Pak1 activation. World J Gastroenterol. 2015 Sep 14; 21(34): 9945-56.

2. Xia C¹, Ma W, Stafford LJ, Marcus S, Xiong WC, Liu M. Regulation of the p21-activated kinase (PAK) by a human Gbeta -like WD-repeat protein, hPIP1. Proc Natl Acad Sci U S A. 2001;  98(11): 6174-9.

3.  Ding XF¹, Shen M, Xu LY, Dong JH, Chen G.

13,14-bis(cis-3,5-dimethyl-1-piperazinyl)-β-elemene, a novel β-elemene derivative, shows potent antitumor activities via inhibition of mTOR in human breast cancer cells. Oncol Lett. 2013; 5(5): 1554-1558.