Microtubule inhibitors anticancer

Taxol is a diterpene alkaloid isolated as an anticancer agent from the bark of T. brevifolia [1]. Subsequently, it was reported that this alkaloid possessed clinical effects for the treatment of leukemia and had excellent efects on refractory ovarian and mammary cancer. The mechanism of action of this alkaloid is to promote the formation of microtubules, the opposite action to that of the microtubule inhibitors hke podophyllotoxin, colchicine, and vinblastine [2,3]. 

Drugs that disturb the assembly and disassembly of microtubules have been widely used to treat various diseases. Indeed, more than 2500 years ago, the ancient Egyptians treated heart problems with colchicine. Nowadays, this drug is used primarily in the treatment of gout and certain other diseases affecting the joints and skin. Other inhibitors of microtubule dynamics, including taxol, are effective anticancer agents and are used in the treatment of ovarian cancer. I... 

It was demonstrated that mitogen-activated protein kinases (MAPKs) were critically involved in the cytotoxicity of CA-4 [50]. CA-4 stimulated both extracellular signal-regulated kinases (ERKl/2) and p38 MAPK in the BEL-7402 hepatocellular carcinoma cell line in a time- and dose-dependent manner. This stimulation was a result of CA-4-induced microtubule disassembly, a reversible process. In authors opinion, these data indicated that p38 MAPK is a potential anticancer target and that the combination of CA-4 with p38 MAPK inhibitors may be a novel and promising strategy for cancer therapy. 

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