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Ref Type Journal Article
PMID (23019217)
Authors Shin JA, Jung JY, Ryu MH, Safe S, Cho SD
Title Mithramycin A inhibits myeloid cell leukemia-1 to induce apoptosis in oral squamous cell carcinomas and tumor xenograft through activation of Bax and oligomerization.
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Abstract Text In several human malignancies, overexpression of myeloid cell leukemia-1 (Mcl-1) confers resistance to induction of apoptosis; however, Mcl-1-mediated inhibition of apoptosis in oral squamous cell carcinoma (OSCC) is not fully understood and has been investigated in this study. The Mcl-1 promoter activators (TPA) and epidermal growth factor (EGF) enhanced neoplastic transformation of JB6 cells and this response was accompanied by enhanced expression of Mcl-1, and knockdown of Mcl-1 by RNA interference (RNAi) decreased JB6 cell transformation. In the same cell line, we also demonstrated that mithramycin A (Mith) decreased TPA-induced JB6 cell transformation and Mcl-1 expression. Mcl-1 was overexpressed in human oral tumors compared with normal oral mucosa and also in several OSCC cell lines including HN22 and HSC-4 cells. Treatment of these cells with Mith also decreased Mcl-1 expression and neoplastic cell transformation, and this was accompanied by induction of several markers of apoptosis. Knockdown of Mcl-1 by RNAi also induced apoptotic cell death. The downregulation of Mcl-1 by Mith and RNAi increased pro-apoptotic protein Bax, resulting in the Bax translocation into mitochondria and its oligomerization. Mith also suppressed tumor growth in vivo and induced apoptosis in tumor by also regulating expression of Mcl-1 and Bax proteins. These indicate a critical role for Mcl-1 in the growth and survival of OSCC and demonstrate that Mith may be a potential anticancer drug candidate for clinical treatment of OSCC.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References