Induction of apoptosis and inhibition of proliferation in colon cancer cells by Salvia fruticosa, Salvia officinalis and rosmarinic acid

Epidemiologic studies have shown that diet and nutrition are key factors associated with colon cancer progression [1]. Plants from the genus Salvia (sage) are known for their wide range of medicinal properties, which include anticancer activity. In view of their high content in bioactive compounds, Salvia could be used in a strategy for cancer prevention as well as a potential source of new antitumor agents. PI3K/Akt and MAPK/ERK signalling pathways play a critical role in cell proliferation and survival and components of these pathways are found frequently altered in colon cancer [2]. The aim of this study was to evaluate the effect of Salvia fruticosa (SF) and Salvia officinalis (SO) water extracts and their main phenolic compound rosmarinic acid (RA) in two human colon carcinoma-derived cell lines, HCT15 and CO115, which have different profiles of constitutive activation of PI3K/Akt and MAPK/ERK pathways. Our results showed that SF, SO and RA were able to induce apoptosis, and sage extracts were also effective in inhibiting cell proliferation (mainly on HCT15 cells), measured by TUNEL and BrdU incorporation assays, respectively. Although both sage extracts and RA did not inhibit Akt phosphorylation measured by western blotting they were able to inhibit ERK phosphorylation in HCT15 cells. Our findings suggest that sage extracts inhibit proliferation in HCT15 cells due to their inhibition on KRAS with a consequent MAPK/ERK pathway downregulation and endorse the use of sage on anticancer therapy/prevention.

Acknowledgements: CPRX and CFL are supported by the FCT grants SFRH/BD/27524/2006 and SFRH/BPD/26316/2006, respectively; and the work was supported by the FCT research grant POCI/AGR/62040/2004.

References: 1. Yang, C.S., Landau, J.M. (2000)J Nutr 130:2409–12.

2. McCubrey, J.A. et al. (2006) Adv Enzyme Regul 46:249–79.