Garcinol, a polyisoprenylated benzophenone modulates multiple pro-inflammatory signaling cascades leading to suppression of growth and survival of head and neck carcinoma
Menée sur des lignées cellulaires de carcinome de la tête et du cou et à l'aide d'une xénogreffe sur un modèle murin, cette étude montre que le garcinol, une substance végétale (Garcinia indica), peut supprimer la croissance et la survie des cellules tumorales en régulant de multiples cascades de signalisation pro-inflammatoire
Constitutive activation of pro-inflammatory transcription factors such as signal transducers and activators of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB) plays a pivotal role in the proliferation and survival of head and neck squamous cell carcinoma (HNSCC). Thus, agents which can modulate deregulated STAT3 and NF-κB activation have a great potential both for the prevention and treatment of HNSCC. In the present report, we investigated the potential effects of garcinol, an active component of Garcinia indica on various inflammatory mediators involved in HNSCC progression using cell lines and xenograft mouse model. We found that garcinol inhibited constitutively activated STAT3 in HNSCC cells in a time and dose dependent manner which correlated with the suppression of the upstream kinases (c-Src, JAK1 and JAK2) in HNSCC cells. Also, we noticed that the generation of reactive oxygen species is involved in STAT3 inhibitory effect of garcinol. Furthermore, garcinol exhibited an inhibitory effect on constitutive NF-κB activation, mediated through the suppression of TGF beta activated kinase 1 (TAK1), and IκB kinase (IKK) activation in HNSCC cells. Garcinol also down-regulated the expression of various gene products involved in cell proliferation, survival, and angiogenesis that led to the suppression of cell proliferation and induction of apoptosis in HNSCC cells. When administered i.p., garcinol inhibited the growth of human HNSCC xenograft tumors in male athymic nu/nu mice. Overall our results suggest for the first time that garcinol mediates its anti-tumor effects in HNSCC cells and mouse model through the suppression of multiple pro-inflammatory cascades.