Targeting COX-2 and NF-kB by Medicinal Herbs as a Potential Therapeutic Strategy

Cumulative experimental and epidemiologic evidence indicates that nuclear factor kappaB (NF- B), a pro-inflammatory transcription factor, plays a significant role in carcinogenesis.

Activation of NF- B was shown to regulate the synthesis of cyclooxygenase-2 (COX-2), as well as other signaling pathways which enhance resistance to apoptosis-based tumor surveillance mechanisms and chemo-radiation therapies. Research aimed at developing chemical and natural inhibitors that block NF- B and COX-2 activation is currently flourishing. Several active ingredients derived from natural compounds, such as curcumin (Turmeric), Reservatol (Grapes), Anethole (Fennell), Bis-eugenol (Cloves), gingeriol (Ginger), ursolic acid (Rosemary), betulinic acid (Platanus acerifolia), Indole-3-carbinol (Kohlrabi), Genistein (Soy plant), Silymarin (Artichok) and Oleandrin (Nerium oleaernd) have shown to inhibit both NF- B and COX-2 activity.

In this study, we assess the ability of several of these agents to potentiate the effect of chemo-radiotherapy. Our results demonstrate that curcumin potentiates the effect of various chemo-radio therapies in CRC, NSCLC and HNSCC cancer cell lines. On the other hand, curcumin did not potentiate the effect of monoclonal anti-EGFR (Cetuximab), anti-Her2 (Herceptin) or the thyrosine kinase inhibitor (Gefetinib) on cancer cells growth. These effects were partially explained by pro-apoptotic mechanisms, and pathways of intracellular cross-talk between EGFR and COX-2.

We believe that therapeutic regimes that include combination of a natural NF- B and COX-2 inhibitors that have a very low profile of side effects, with chemo-radio therapy present one of the promising avenues in cancer treatment.

Shahar Lev-ari, Gideon Earon, liron Berkovich, Ilan Ron

Laboratory of Herbal Medicine and Cancer Research,

Tel-AvivMedicalCenter,Tel-Aviv, Israel.