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Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade
Published on: August 14, 2019
The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells
Sara Jaramillo1, Sergio Lopez, Lourdes M Varela
1Laboratory of Cell Wall and Functional Components of Foods, Instituto de la Grasa (CSIC), 41014 Seville, Spain.
Abstract:
The aim of this study was to determine whether isorhamnetin, an immediate 3'-O-methylated metabolite of quercetin, affects proliferation, cell death, and the cell cycle of human colon carcinoma (HCT-116) cells. Isorhamnetin was found to be a potent antiproliferative agent in a dose- and time-dependent manner, with an IC50 of 72 μM after 48 h of incubation as estimated by MTT assay. Flow cytometry and fluorescence microscopy analysis showed that isorhamnetin exerted a stimulatory effect on apoptosis and necrosis. Isorhamnetin also increased the number of cells in G2/M phase. Serum deprivation appeared to potentiate the effects of isorhamnetin on cell death and facilitated cell cycle progression to G0/G1 phase. These results suggest that isorhamnetin might mediate inhibition of HCT-116 cell growth through the perturbation of cell cycle progression and are consistent with the notion that G2/M checkpoints could be a conserved target for flavonoids in human colon cancer cells, leading to apoptotic and necrotic death. These antiproliferative, apoptotic, necrotic, and cell cycle effects suggest that isorhamnetin may have clinically significant therapeutic and chemopreventive capabilities. To our knowledge, this is the first report of the effect of isorhamnetin on human colon cancer cells.
Insights
Isorhamnetin, a quercetin metabolite, effectively inhibits human colon cancer (HCT-116) cell growth by inducing cell death and altering the cell cycle. This study highlights its potential as a therapeutic and chemopreventive agent.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Quercetin metabolites, such as isorhamnetin, are investigated for their biological activities.
- Colon cancer remains a significant global health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects of isorhamnetin on human colon carcinoma (HCT-116) cell proliferation, cell death, and cell cycle.
- To explore the potential therapeutic and chemopreventive applications of isorhamnetin in colon cancer.
Main Methods:
- MTT assay to determine antiproliferative effects and IC50 values.
- Flow cytometry and fluorescence microscopy to analyze apoptosis, necrosis, and cell cycle distribution.
- Incubation of HCT-116 cells with isorhamnetin under normal and serum-deprived conditions.
Main Results:
- Isorhamnetin demonstrated potent, dose- and time-dependent antiproliferative activity against HCT-116 cells (IC50 = 72 μM at 48 h).
- Isorhamnetin induced apoptosis and necrosis in HCT-116 cells.
- Isorhamnetin treatment led to an accumulation of cells in the G2/M phase of the cell cycle.
- Serum deprivation enhanced isorhamnetin's effects on cell death and promoted cell cycle progression to G0/G1 phase.
Conclusions:
- Isorhamnetin inhibits HCT-116 cell growth by perturbing cell cycle progression, potentially targeting G2/M checkpoints.
- The findings suggest that isorhamnetin possesses significant antiproliferative, apoptotic, and necrotic properties.
- Isorhamnetin shows promise for clinical therapeutic and chemopreventive applications in human colon cancer.
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