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Background: Galbanic acid (GBA) is a sesquiterpene coumarin with valuable pharmacological effects. Adult T-cell lymphoma (ATL) is an aggressive lymphoid malignancy with low survival rate. Although arsenic trioxide (ATO) is a standard therapeutic agent for ATL treatment, efficacy of chemotherapy is limited due to chemoresistance of cells. Objective: The present study was carried out to investigate whether GBA in combination with ATO would improve cytotoxicity against ATL cells. Methods: GBA was isolated from the roots of Ferula szowitsiana by column chromatography on silica gel. MT-2 cells were treated with 20 µM GBA + 4 µM ATO and viability was evaluated by alamarBlue assay. Cell cycle was analyzed by PI staining, while the activity of P-glycoprotein (P-gp) was evaluated by mitoxantrone efflux assay. To understand the molecular mechanisms of GBA effects, the expression of NF-κB (RelA), P53, CDK4, c-MYC, c-FLIPL and c-FLIPS was evaluated by real-time PCR. Results: Combinatorial use of GBA + ATO significantly reduced the viability of MT-2 cells, and induced cell cycle arrest in the sub-G1 phase. GBA improved mitoxantrone accumulation in cells, indicating that this agent has inhibitory effects on the functionality of P-gp efflux pump. Moreover, real-time PCR analysis revealed that GBA + ATO negatively regulated the expression of P53, CDK4, c-FLIPL and c-FLIPS. Conclusion: Due to the interesting effects of GBA on the accumulation and toxicity of ATO, combinatorial use of these agents could be considered as a new therapeutic approach for ATL treatment.

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with two life-threatening diseases; HAM/TSP and ATLL. Due to the slow-growing HTLV-1 infection worldwide, WHO urged for elimination. A large border with Afghanistan, northeast Iran is an endemic region for HTLV-1 infection. Historically, Afghanistan has common sociocultural similarities to Persian peoples. This study was conducted to evaluate HTLV-1 prevalence in Afghan refugees. Also, the HTLV-1 transmission rate and understanding of whether or not the Silk Road has been the route of HTLV-1 infection to Iran were investigated. This case-control study was conducted in a rural area of Fariman city, with Afghan residents who migrated around 165 years ago, from 1857, the Treaty of Paris at the end of the Anglo-Persian war, and a refugee camp in Torbat-e-Jam city. These populations in HTLV-1 endemic area were compared to a segregated population of Afghan refugees in Semnan, the centre of Iran. Blood samples of 983 volunteers were assessed with the ELISA method for the presence of HTLV-1 antibodies and then confirmed by PCR technique. All samples from Afghan refugee camps, Semnan and Torbat-e-Jam, were negative for HTLV-1 infection. However, the prevalence of HTLV-1 infection in Fariman, a rural population of Afghan origin, was approximately 2.73%. The results showed that HTLV-1 is not endemic in Afghanistan, a war-stricken region with refugees distributed worldwide. The land Silk Road has not been the route of HTLV-1 transmission to Northeastern Iran. Importantly, HTLV-1 endemicity might occur during a long time of living in an endemic area.