title: Antitumor activity of acriflavine in human hepatocellular carcinoma cells.
abstract: Patients suffering from advanced hepatocellular carcinoma can generally be treated only by targeted therapy to achieve a survival rate that lasts a few months more than that achieved with conventional therapy. To develop better drugs against hepatocellular carcinoma, we screened a variety of compounds and treated four human hepatocellular carcinoma (HCC) cell lines with different drug concentrations. We then examined cell viability using the MTT assay. Results show that a new candidate drug, acriflavine (ACF), suppresses the viability of HCC cell lines in a dose-dependent manner. Flow cytometry analysis reveals that ACF significantly induces the accumulation of a Sub-G1 population of Mahlavu cells. Moreover, ACF decreases Bcl-2 expression and caspase-3 activation. The content of cleaved poly-(ADP-ribose)polymerase-1 (PARP-1) is significantly increased. These findings suggest that ACF suppresses HCC cell growth through the caspase-3 activation pathway. Compared to clinically-approved drugs, the IC50 of ACF (1 μM) is nearly ten-fold lower than that of sorafenib (13 μM). In the in vivo test, nude mice received Mahlavu cell xenografts subcutaneously and were randomly assigned into two groups: control and experimental groups. Treatment was initiated 3 days after implantation and intraperitoneal injection of 0.9 % normal saline or 2 mg/Kg of ACF was continued daily for five weeks. Tumors were palpable in vehicle-treated mice by day 3 and grew to approximately 2000 mm3 by the end of the experiment, whereas mice treated with ACF experience tumor growth to approximately 500 mm3. We, thus, suggest that ACF can inhibit cell growth in HCC cells. Our results may assist the delineation of the mechanism(s) leading to HCC cell growth inhibition and provide a new target therapy capable to prolong the survival rate of patients in advanced stage.
authors: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: Chia-Jen
authors: CJ
authors: Lee
authors: Department of Surgery, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C.
authors: Chia-Herng
authors: CH
authors: Yue
authors: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, R.O.C.
authors: Yu-Yu
authors: YY
authors: Lin
authors: Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan, R.O.C. jyl@mail.cmu.edu.tw jcwu@vghtpe.gov.tw.
authors: Jaw-Ching
authors: JC
authors: Wu
authors: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, R.O.C. jyl@mail.cmu.edu.tw jcwu@vghtpe.gov.tw.
authors: Jer-Yuh
authors: JY
authors: Liu
mesh_terms: D000167:Acriflavine / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000167:Acriflavine
keywords: Acriflavine; Mahlavu; hepatocellular carcinoma