Chronic Sulforaphane Application Does Not Induce Resistance in Renal Cell Carcinoma Cells

Since the natural compound sulforaphane (SFN) has been shown to stop tumor growth, renal cell carcinoma (RCC) patients often use this drug in addition to their prescribed oncotherapy. The aim of this study was to examine whether resistance to SFN may develop after long-term application.

Several RCC cell lines were incubated with SFN for short periods of time (24-72 h) or long periods of time (8 weeks) and cell growth, proliferation, and cell-cycle proteins were analyzed.

Both short- and long-term application of SFN distinctly reduced RCC cell growth and proliferation. However, differences in the distribution of cells in each phase of the cell cycle and in the expression of cell-cycle proteins were apparent. Short-term treatment induced S-phase arrest, whereas long-term treatment induced G₀/G₁-phase arrest. Expression of Cdk1 and Cdk2 increased over short-term incubation, but decreased long-term. Expression of pCdk2, Akt, and Raptor were reduced following long-term SFN-exposure, but remained unchanged when SFN was applied for short periods of time.

Chronic use of SFN did not evoke resistance, but differentially altered signaling pathways, compared to short-term use.