title: Isorhamnetin suppresses colon cancer cell growth through the PI3K‑Akt‑mTOR pathway.
abstract: Isorhamnetin, a flavonoid isolated from the fruits of herbal medicinal plants, such as Hippophae rhamnoides L., exerts anticancer effects similar to other flavonoids. However, the effect of isorhamnetin on colorectal cancer (CRC) and the underlying molecular mechanism are unclear. This study aimed to determine the effect of isorhamnetin on the proliferation of cells from the human CRC cell lines, HT‑29, HCT116 and SW480. It was demonstrated that isorhamnetin suppressed the proliferation of cells from all three cell lines, induced cell cycle arrest at the G2/M phase and suppressed cell proliferation by inhibiting the PI3K‑Akt‑mTOR pathway. Isorhamnetin also reduced the phosphorylation levels of Akt (ser473), phosph‑p70S6 kinase and phosph‑4E‑BP1 (t37/46) protein, and enhanced the expression of Cyclin B1 protein. Therefore, this compound was revealed to be a selective PI3K‑Akt‑mTOR pathway inhibitor, and may be a potent anticancer agent for the treatment of CRC, as it restrains the proliferation of CRC cells.
authors.affiliation: Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D056744:Cyclin B1 / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D031281:Hippophae / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D056744:Cyclin B1; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D011794:Quercetin; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C087000:EIF4EBP1 protein, human; C047368:3-methylquercetin; C546842:MTOR protein, human