Abstract
Using comparative proteomic analysis, we investigated the synergistic suppressive activity of natural components on the metastasis of colorectal cancer (CRC) cells. The isogenic SW480 and SW620 colon adenocarcinoma cell lines were compared to identify proteins overexpressed in metastatic SW620, which demonstrated altered expression levels following treatment with bioactive food components from natural sources and/or chemotherapeutic agents. SW620 cells were treated with three natural components, namely, curcumin, luteolin, and ginsenoside 20(S)‐Rg3 and three chemotherapeutic agents, 5‐fluorouracil, sorafenib, and oxaliplatin, which were selected by their cytotoxicity to SW620 cells. Comparative proteomic datasets were generated using linear ion‐trap mass spectrometry combined with nano‐flow ultra performance liquid chromatography. MS data files were searched using the SEQUEST algorithm. Significant overexpression of structural proteins, such as neurofilaments and histone proteins, was observed in untreated SW620 compared to untreated SW480 cells. Interestingly, treatment with curcumin or ginsenoside 20(S)‐Rg3 suppressed the overexpression more effectively than either 5‐FU or oxaliplatin, which are drugs currently used as primary therapy in the treatment of colorectal cancer. In addition, the overexpression of histone proteins in SW620 cells was down‐regulated by the co‐treatment of curcumin and oxaliplatin, which demonstrated synergistic cytotoxicity via combinational treatment. It has been known that chemical modification (e.g. acetylation) of histones is one of the major features of cancer metastasis. However, based on the current proteomic analysis, increased expression of histone proteins is also associated with the development of CRC metastasis. Furthermore, our data suggests that curcumin co‐treatment represents a promising adjuvant to standard oxaliplatin therapy for the suppression of metastasis in colorectal adenocarcinoma.
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