Inhibition of Molecular Signaling in Huh-7 Cells by AM3: A Novel Chemotherapeutic Agent for Hepatocellular Carcinoma

Background: According to a review of recent literature, no previous studies have reported the dose-dependent selective inhibition of the antiproliferative activity using colony and sphere formation assays and immunoblotting in human hepatoma cells in response to doxorubicin and mitoxantrone structural analogs such as AM3. <p></p> Objective: We evaluated the anticancer activity of mitoxantrone (MIT) structural analogs 1,5-bis({2- [(2-hydroxyethyl) amino]ethyl}-amino)-anthracene-9,10-dione (AM3) in human hepatoma cells (Huh-7). <p></p> Methods: In this paper, we synthesized AM3 through the nucleophilic amino substitution of 1,5- dichloroanthraquinone with the corresponding dichloride groups under microwave-accelerated heating. The structural characteristics of AM3 were analyzed through ultraviolet–visible spectroscopy and nuclear magnetic resonance. In vitro activity of AM3 was measured using the dose-dependent selective inhibition of the antiproliferative activity using colony and sphere formation assays and immunoblotting in Huh-7. <p></p> Results: The antiproliferative activity of AM3 was determined using IC50 values as 2.03 and 1.70 µM for hepatocellular carcinoma cell lines Huh-7 and SK-Hep-1 cells, respectively. In addition, colony formation assay of Huh-7 cells revealed that AM3 significantly suppressed the mean colony formation rate from 99.9 % to 2.5 %, and growth inhibition rate of sphere cells was significant, in which 5.0 µ M of AM3 inhibited up to 28.5 % cell growth in the Huh-7 sphere cells. Immunoblotting confirmed the overexpression of CD44, COX-2, p-Akt, and Akt. <p></p> Conclusion: Thus, AM3 is a novel therapeutic agent for suppressing cancer stemness and inflammation signaling in Huh-7 cells. <p></p>

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