Objectives: Indoleamine-2,3-dioxygenase (IDO) is a heme enzyme that initiates the oxidative degradation of the essential amino acid L-tryptophan, along the kynurenine pathway. The local cellular depletion of L- tryptophan that results, may enable the host to inhibit the growth of various infectious pathogens in vivo. In addition to its function as an important immune control enzyme, the involvement of IDO in the growth inhibition and/or apoptosis of different cell types including T cells has been reported. The aim of this study was to determine whether IDO is involved in the modulation of growth inhibition of head and neck squamous cell carcinoma (HNSCC) mediated by anti-cancer agents. Methods: RT-PCR, QRT-PCR, Western Blot analysis, MTT assay Results: The treatment of HNSCC cell lines with anti-cancer agents (TNF-alpha, Cisplatin, Anti-Fas antibody, Taxol and Bortezomib) was found to inhibit cell growth in different HNSCC cell lines. Data obtained from RT-PCR, QRT-PCR and MTT-assay demonstrated that anti-cancer agents mediated cell growth inhibition is associated with the induction of IDO gene expression. The inhibition of IDO gene expression by specific siRNA`s resulted in the abrogation of anti-cancer agents-induced cell growth inhibition of HNSCC. These data suggest the involvement of IDO in the modulation of anti-cancer agents-induced cell growth inhibition of HNSCC. Conclusions: Our data provide evidence for the involvement of indoleamine-2,3-dioxygenase (IDO) in modulation of anti-cancer agent(s)-induced effects in HNSCC and suggest further, a key role for IDO in tumour therapy

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