title: Apigenin up-regulates transgelin and inhibits invasion and migration of colorectal cancer through decreased phosphorylation of AKT.
abstract: Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world. Apigenin is a flavonoid that possesses various clinically relevant properties such as anti-tumour, anti-platelet and anti-inflammatory activities. Our results showed that apigenin has anti-proliferation, anti-invasion and anti-migration effects in three kinds of colorectal adenocarcinoma cell lines, namely SW480, DLD-1 and LS174T. Proteomic analysis with SW480 indicated that apigenin up-regulated the expression of transgelin (TAGLN) in mitochondria to exert its anti-tumour growth and anti-metastasis effects. Real-time quantitative polymerase chain reaction (RQ-PCR) and western blot confirm the up-regulation in all the three colorectal adenocarcinoma cells. An inverse correlation was observed between TAGLN expression and CRC metastasis in tissue microarray staining. TAGLN siRNA increased the viability of SW480. Apigenin decreased the expression of MMP-9 in a dose-dependent manner. Transfection of three truncated forms of TAGLN and wild type has identified TAGLN as a repressor of MMP-9 expression. A synergetic effect was observed in overexpression of TAGLN wild type and apigenin treatment which manifested as lowered phosphorylation of AKT Ser473 and ATK Thr308. In an orthotopic CRC model, apigenin inhibited tumour growth and metastasis to liver and lung. In conclusion, our research provided direct evidence that apigenin inhibited tumour growth and metastasis both in vitro and in vivo. Apigenin up-regulated TAGLN and hence down-regulated MMP-9 expression through decreasing phosphorylation of Akt at Ser473 and in particular Thr308 to prevent cell proliferation and migration.
authors.affiliation: Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Taishan People's Hospital, Taishan 529200, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chunhua
authors.forename: Lin
authors.initials: L
authors.lastname: Donglan
authors.forename: Fu
authors.initials: F
authors.lastname: Xiuqiong
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lihua
authors.forename: Fan
authors.initials: F
authors.lastname: Qin
authors.forename: Liu
authors.initials: L
authors.lastname: Yawei
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liang
authors.forename: Wen
authors.initials: W
authors.lastname: Ge
authors.forename: Jing
authors.initials: J
authors.lastname: Linlin
authors.forename: Zeng
authors.initials: Z
authors.lastname: Ping
authors.forename: Li
authors.initials: L
authors.lastname: Kun
authors.forename: Sun
authors.initials: S
authors.lastname: Xuegang
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000473:pathology*; D015536:Down-Regulation; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008840:Microfilament Proteins / Q000096:biosynthesis*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; C051615:transgelin; D047310:Apigenin; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9
keywords: AKT; Apigenin; Colorectal cancer; Invasion; Migration; Transgelin