Mithramycin A (Mith A), an older chemotherapy drug, has been studied as a potential therapeutic agent that may possess anti-tumor activity as well as apoptotic effect in several cancer patients. No related research has been done on the apoptotic effect of Mith A in HN22 and HSC4 oral squamous cancer cells using the specificity protein 1 (Sp1) protein. Hence, here we investigated whether Mith A can inhibit cell growth and regulate Sp1 target proteins by suppressing levels of Sp1 protein in HN22 and HSC4 cells. As a result, oral squamous cancer cell viability was reduced and apoptotic cell death was increased by Mith A. IC₅₀ of Mith A for 48 h treatment in the HN22 and HSC4 cells were calculated to be approximately 25 and 26 nM. Mith A significantly suppressed Sp1 protein expression levels and modulated the expression level of the Sp1 regulatory protein such as p27, p21, cyclin D1, Mcl-1, and survivin in HN-22 and HSC-4 cells. Mith A also induced apoptotic signaling molecules, including: cleavages of Bid, caspase-3, and PARP, and upregulation of Bax in HN22 and HSC4 cells. In conclusion, our results strongly suggest that Mith A regulated proliferation and mediated apoptosis through inhibition of Sp1 in oral squamous cancer cells. (Cancer Prev Res 17, 0-217, 2012)

Keywords: Mithramycin A, Specificity protein 1, Oral squamous cancer, Apoptosis