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Anti‐invasive effect and pharmacological mechanism of genistein against colorectal cancer
Author(s) -
Chen Xiaoyu,
Wu Youjun,
Gu Junzhao,
Liang Ping,
Shen Meizhen,
Xi Jiaxi,
Qin Jian
Publication year - 2020
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1627
Subject(s) - protein kinase b , genistein , cancer research , mapk/erk pathway , pi3k/akt/mtor pathway , metastasis , cancer , colorectal cancer , apoptosis , medicine , cell growth , p38 mitogen activated protein kinases , pharmacology , kinase , biology , microbiology and biotechnology , biochemistry
Colorectal cancer (CRC) refers to a deadly carcinoma following potent invasiveness and metastasis in advanced stage. Unfortunately, existing anti‐CRC medicine is insufficient for chemotherapy in addition to adverse effects. Consequently, the candidate natural ingredient for treating CRC needs to be further developed. Our previous experiments report that genistein exerts beneficial effects to inhibit CRC cells via an antiproliferative mechanism. Based on the metastatic characteristics of staging CRC, anti‐invasive and antimetastatic pharmacological activities using genistein remain uninvestigated. The scientific purpose of this study was to disclose the antimetastatic mechanism by using human and cell culture/nude mice samples, followed by biochemical tests and immunoassays. In human study, these CRC cases resulted in increased transforming growth factor beta‐1 (TGF‐β1) levels, long noncoding RNA (lncRNA) TTTY18 expressions, followed with up‐regulated Ki‐67, serum and glucocorticoid regulated kinase 1 (SGK1), Akt Ser473 expressions. In a study in vitro, genistein‐dosed CRC cells showed suppressed cell viability, promoted cell apoptosis, reduced Ki‐67 positive cells, reduced cellular migration, down‐regulated expressions of TTTY18, SGK1, Akt Ser473 , p38 MAPK Tyr323 . In a further study in vivo, genistein‐dosed tumor‐bearing nude mice exhibited visibly reduced body mass, lowered tumorous TGF‐β1 and TTTY18 contents. In addition, intracellular numbers of SGK1, Akt Ser473 , p38 MAPK Tyr323 positive cells were reduced dose‐dependently. Collectively, these human and experimentative findings reveal that genistein pharmacologically exerts the potential antimetastatic CRC effects, possibly through a molecular mechanism of inhibiting TTTY18/Akt pathway in CRC cells.