Saponins extracted from by-product of Asparagus officinalis L. suppress tumour cell migration and invasion through targeting Rho GTPase signalling pathway

Introduction

The global burden of cancer is still increasing and it is the leading cause of death in economically developed countries. About 12.7 million new cases and 7.6 million cancer deaths are estimated to have occurred in 2008 worldwide. Most cancers can be cured surgically before cancer metastasis, and 5 year survival rates are often above 90%. However, once metastasis has taken place, the 5 year survival rate falls below 15%. The process of cancer metastasis consists of a series of sequential and discrete steps. The malignant cells first escape from a primary tumour, then spread through the blood and lymph vessels to a secondary site and finally form secondary tumours. Therefore early treatment to block cancer cell metastasis is paramount.

Ras homologue GTPases (Rho GTPases) are small molecules of the Ras superfamily. They share structural homology with a Rho-type GTPase-like domain located between the fifth βstrand and the fourth α-helix within the small GTPase domain. A structural feature differentiates the Rho proteins from other small GTPases. The Rho family can be simply divided into six subfamilies, including the RhoA-related subfamily (RhoA, RhoB and RhoC), the Rac1-related subfamily (Rac1 (and Rac1b), Rac2, Rac3 and RhoG), the Cdc42-related subfamily (Cdc42 (and G25K), TC10, TCL, Chp/Wrch-2 and Wrch-1), the Rnd subfamily (Rnd1, Rnd2 and RhoE/Rnd3) and the RhoBTB subfamily.5 Research has revealed that Rho GTPases play an acknowledged role in cell motility, showing that they act to regulate cell adhesions and cytoskeleton networks. Among them, RhoA, Cdc42 and Rac1 are three classical and well-studied members. RhoA promotes actin/myosin contractility and the formation of stress fibres and focal adhensions, Cdc42 causes the formation of filopodia, regulates cell polarity and thereby maintains the directionality of cell movement, while Rac1 promotes actin polymerisation and the formation of lamellipodia.