Oncogenic Phenotypes in K-Ras Transformed Cells

Genetic mutations in K-Ras, an oncogene belonging to the Ras protein superfamily, are present in number of cancers, including over 90% of pancreatic and 50% of colorectal cancers. The mutated or oncogenic form of the K-Ras GTPase is perpetually locked in the GTP-bound active conformation, thereby inducing extreme and rapid cell proliferation as well as decreasing cell sensitivity to suspension-induced cell death, or anoikis. These two phenotypes are highly characterized traits of oncogenic cells. Ruthenium-derived potential anticancer drugs have previously been shown to exhibit anti-metastasic properties at a lower cytotoxicity than current metallopharmacueticals, such as the platimun-based cisplatin. This study examined the possible anti-metastatic effects of two ruthenium-based drugs, NAMI-A (imidazolium transimidazoledimethylsufoxide-tetrachlororuthenate) and KP1019 (indazolium trans[tetrachlorobis(1H-indazole)ruthenate(III)] on oncogenic K-Ras Rat Intestinal Epithelial (RIE-1) cells. The addition of NAMI-A or KP1019 to chronically active K-Ras RIE-1 cells did not demonstrate increased sensitivity to anoikis, while it did affect the cell proliferation in both cases.