ReferenceID 5266
Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B
Pharmaceutics
Fraxetin is a coumarin scaffold compound extracted from Fraxinus rhynchophylla. It has antioxidant, anti-inflammatory, hepatoprotective, and antifibrotic effects. Furthermore, fraxetin has anticancer effects in breast an
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Record Fields
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- Reference Id
- 5266
- Evidence Id
- 21856
- Core Evidence Id
- 21856
- Source Reference Id
- 3793
- Herb2 Reference Id
- HBREF004590
- Subject Paper Key
- HBIN026733_33477262
- Pubmed Id
- 33477262
- Doi
- 10.3390/pharmaceutics13010112
- Paper Title
- Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B
- Paper Abstract
- Fraxetin is a coumarin scaffold compound extracted from Fraxinus rhynchophylla. It has antioxidant, anti-inflammatory, hepatoprotective, and antifibrotic effects. Furthermore, fraxetin has anticancer effects in breast and lung cancer. We aimed to evaluate whether fraxetin has anticancer activity in hepatocellular carcinoma (HCC) cells and its underlying mechanism. We demonstrated the anticancer effects of fraxetin in the HCC cell lines Huh7 and Hep3B. We confirmed that fraxetin inhibited cell proliferation (42% +- 10% Huh7; 52% +- 7% Hep3B) by arresting the cell cycle and inducing apoptosis in both cell lines. Moreover, fraxetin increased reactive oxygen species production (221% +- 55% Huh7; 460% +- 73% Hep3B), depolarized the mitochondrial membranes (DeltaPsim) (345% +- 160% Huh7; 462% +- 140% Hep3B), and disrupted calcium homeostasis in both HCC cell lines. Chelating calcium ions with BAPTA-AM restored proliferation in fraxetin-treated Huh7 cells but not in Hep3B cells. Fraxetin did not affect the phosphorylation of extracellular-signal-regulated kinase 1/2, whereas it decreased JNK and phosphoinositide 3-kinase signaling. Furthermore, fraxetin and mitogen-activated protein kinase pharmacological inhibitors had synergistic antiproliferative effects on HCC cells. Although our study was limited to in vitro data that require validation, we suggest that fraxetin is a potential therapeutic agent against HCC progression.
- Journal
- Pharmaceutics
- Publish Year
- 2021
- Experiment Subject
- cell lines; fraxetin-treated huh7 cells; hcc cell lines; hep3b; hep3b cells; huh7
- Experiment Type
- Cell Experiment
- Phenotype Related
- Breast And Lung Cancer; Hepatocellular Carcinoma
- Paper Title Cn
- Paper Title En
- Fraxetin Suppresses Cell Proliferation and Induces Apoptosis through Mitochondria Dysfunction in Human Hepatocellular Carcinoma Cell Lines Huh7 and Hep3B
- Bilingual Status
- semi_complete