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Isorhamnetin suppresses colon cancer cell growth through the PI3K‑Akt‑mTOR pathway
Chuan Li1, Xi Yang1, Cheng Chen1
1Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
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.
Insights
Isorhamnetin, a flavonoid from medicinal plants, effectively inhibits colorectal cancer (CRC) cell proliferation. It works by blocking the PI3K-Akt-mTOR pathway, showing potential as a novel CRC treatment.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- Flavonoids, like isorhamnetin found in Hippophae rhamnoides L., exhibit anticancer properties.
- The specific impact of isorhamnetin on colorectal cancer (CRC) and its molecular mechanisms remain largely uninvestigated.
Purpose of the Study:
- To investigate the antiproliferative effects of isorhamnetin on human CRC cell lines (HT-29, HCT116, SW480).
- To elucidate the molecular pathways targeted by isorhamnetin in CRC cells.
Main Methods:
- Treatment of HT-29, HCT116, and SW480 cells with isorhamnetin.
- Cell cycle analysis to determine phase arrest.
- Western blot analysis to assess protein expression and phosphorylation levels within the PI3K-Akt-mTOR pathway.
Main Results:
- Isorhamnetin significantly suppressed proliferation across all tested CRC cell lines.
- The compound induced cell cycle arrest at the G2/M phase.
- Inhibition of the PI3K-Akt-mTOR pathway was observed, with reduced phosphorylation of Akt, p70S6 kinase, and 4E-BP1, alongside increased Cyclin B1 expression.
Conclusions:
- Isorhamnetin demonstrates selective inhibition of the PI3K-Akt-mTOR pathway in CRC cells.
- This flavonoid exhibits potential as a therapeutic agent for colorectal cancer by restraining cancer cell proliferation.
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