Ruta graveolens extract induces DNA damage pathways and blocks Akt activation to inhibit cancer cell proliferation and survival.

ABSTRACT

BACKGROUND: Ruta graveolens is a medicinal herb that has been used for centuries against various ailments. This study examined the anticancer properties of the herb using cancer cell lines. MATERIALS AND METHODS: Methanolic extract of R. graveolens was tested on colon, breast and prostate cancer cells. Viability, cell cycle profiles, clonogenicity and capase activation were measured. Induction and subcellular localizations of p53, 53BP1 and γ-H2AX proteins were examined. RESULTS: The extract dose-dependently decreased the viability and the clonogenicity of treated cells and induced G2/M arrest, aberrant mitoses, and caspase-3 activation. It also induced the p53 pathway and focal concentration of the DNA damage response proteins 53BP1 and γ-H2AX. Moreover, the levels of phospho-Akt and cyclin B1 were reduced by treatment, whereas only cyclin B1 was reduced in normal dermal fibroblasts. CONCLUSION: R. graveolens extract contains bioactive compounds which, independently of known photoactivatable mechanisms, potently inhibit cancer cell proliferation and survival through multiple targets.