ReferenceID 2411
Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis
Acta Pharm Sin B
Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root
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Record Fields
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- Reference Id
- 2411
- Evidence Id
- 19001
- Core Evidence Id
- 19001
- Source Reference Id
- 4841
- Herb2 Reference Id
- HBREF005638
- Subject Paper Key
- HBIN035541_32963939
- Pubmed Id
- 32963939
- Doi
- 10.1016/j.apsb.2020.06.015
- Paper Title
- Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis
- Paper Abstract
- Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Salvia miltiorrhiza Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out GSDME switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC via GSDME-dependent pyroptosis.
- Journal
- Acta Pharm Sin B
- Publish Year
- 2020
- Experiment Subject
- mouse; hepa1-6 cells; hepatocellular carcinoma (hcc) cell line; hepg2
- Experiment Type
- Cell Experiment
- Phenotype Related
- Tumor; Pyroptosis; Hepatocellular Carcinoma; Tumors
- Paper Title Cn
- Paper Title En
- Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis
- Bilingual Status
- semi_complete