Influence of anti-colorectal cancer phytochemicals on Pyruvate Kinase M2 in SW620 cell line

• Main Authors: Pei-Yu Shih, 施姵妤
• Other Authors: 蔣丙煌
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/52208736256195282884

碩士 === 國立臺灣大學 === 食品科技研究所 === 101 === Colorectal cancer (CRC) is the most common cancer in Taiwan and the incidence of CRC was dramatically raised during the past few decades. Recent studies demonstrated that pyruvate kinase M2 (PKM2) is the predominant PK isoform in tumor and supports growth advantage in tumorigenesis. In the cytoplasm, high activity PKM2 helps to generate enough energy and low activity PKM2 satisfies the anabolic demands of macromolecular biosynthesis. In addition to well-established role in the metabolic reprogramming in the cytoplasm, PKM2 is also shown to participate in regulation of oncogene transcription in the nucleus. Furthermore, PKM2 would promote high proliferation rate and malignant grade in CRC development. Clinical studies also showed that the increased PKM2 expression is highly associated with poor prognosis and high risk death in CRC patient. Since there are many phytochemicals have been reported with anti-CRC properties, but their bioactivities on regulating PKM2 have not been sufficiently investigated. Thus, the objective of this study was to investigate the effects of four potential anti-CRC phytochemicals, including Curcumin, Quercetin, Resveratrol and Pterostilbene on PKM2 in human CRC cell SW620. The results showed that all of the four phytochemicals could effectively suppress the total PKM2 expression and regulate the distribution of intracellular PKM2. Quercetin is the most effective phytochemical, resulting in a 66% inhibition of the total PKM2 protein level, followed by Resveratrol which has 44% inhibition ability. The third place is Curcumin, it reduces 24% expression of PKM2. The last one is Pterostilbene which tends to down-regulate expression of PKM2 but without significant difference statistically. Moreover, the decrease of PKM2 protein expression due to the four phytochemicals treatments may via inhibition of the expression of c-Myc and HIF-1α. Our results also showed that the four phytochemicals have abilities to reduce the nuclear PKM2 level and thereby inhibit the expression of nuclear PKM2 downstream target protein MEK5. Consequently, phytochemicals may suppress the total PKM2 expression and regulate the distribution of intracellular PKM2 to inhibit CRC cell proliferation. It seems that the PKM2-mediated effect of phytochemicals on cancer progression can provide a new dimension to cancer treatment.