| Summary: | <p>Abstract</p> <p>Background</p> <p><it>Crassocephalum crepidioides</it>, a plant distributed in Okinawa Islands, is known in folk medicine; however, its anticancer activity has not been investigated. The aim of this study was to determine the <it>in vitro</it> and <it>in vivo</it> antitumor activities of <it>C. crepidioides</it> on murine Sarcoma 180 (S-180) and related molecular mechanisms.</p> <p>Methods</p> <p>The antitumor effect of <it>C. crepidioides</it> was evaluated in S-180-cell-bearing mice. Cell growth was assessed using a colorimetric assay. Nitrite and nitrate levels were measured by colorimetry. The expression levels of inducible NO synthase (iNOS) in murine RAW264.7 macrophages was assessed by reverse transcriptase-polymerase chain reaction. Activation of iNOS promoter was detected by reporter gene. Activation of nuclear factor-κB (NF-κB) was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling was analyzed using inhibitors of NF-κB and dominant-negative mutants, and Western blot analysis.</p> <p>Results</p> <p><it>C. crepidioides</it> extract delayed tumor growth in S-180-bearing mice. However, it did not inhibit S-180 cell growth <it>in vitro</it>. Supernatant of cultured <it>C. crepidioides</it>-stimulated RAW264.7 macrophages was cytotoxic to S-180 cells. This cytotoxicity was associated with nitric oxide (NO) production. NF-κB signaling pathway was crucial for the transcriptional activation of iNOS gene. Isochlorogenic acid, a component of <it>C. crepidioides</it>, induced NF-κB activation and iNOS expression.</p> <p>Conclusions</p> <p>The results highlight the oncolytic and immunopotentiation properties of <it>C. crepidioides</it> mediated through NF-κB-induced release of NO from macrophages.</p>
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