Here　we　showed　that　ursolic　acid　(UA),　a　pentacyclic　triterpene　natural　product,　and　its　novel　prodrug　derivative　US597　suppressed　cancer　cells　adhesion,　invasion　and　migration.　This　effect　was　accompanied　by　inhibition　of　focal　adhesion　signaling　pathway　including　alterations　in　ICAM-1,　VCAM-1,　E-selectin,　P-selectin,　integrin　alpha　6　beta　1,　FAK,　Src,　paxillin　and　PTEN.　While　oral　administration　of　UA　or　US597　increases　survival　rate　of　melanoma　lung　metastasis　in　C57BL/6　mice,　US597　treatment　extend　the　survival　rate　above　that　of　UA.　Immunohistochemical　analysis　revealed　that　US597　treatment　regulates　ICAM-1,　a　biomarker　of　metastasis.　We　did　not　detect　side　effects　with　US597　in　mice　such　as　weight　loss,　viscera　tissues　toxicity　and　blood　cell　abnormalities.　Thus,　UA　and　US597　are　potential　drug　candidates　for　preventing　cancer　metastasis.　Molecular　and　cellular　study　data　suggest　that　UA　and　US597　modulate　expression　of　cell　adhesion　molecules　within　focal　adhesion　signaling　pathway　leading　to　cancer　cell　motility.