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Anti-proliferative Effect of 15,16-Dihydrotanshinone I Through Cell Cycle Arrest and the Regulation of AMP-activated Protein Kinase/Akt/mTOR and Mitogen-activated Protein Kinase Signaling Pathway in Human Hepatocellular Carcinoma Cells
Journal of Cancer Prevention ; : 63-69, 2018.
Article in English | WPRIM | ID: wpr-740103
ABSTRACT

BACKGROUND:

15,16-dihydrotanshinone I (DHTS) is a natural abietane diterpenoid that is mainly found in the roots of Salvia miltiorrhiza Bunge (Labiatae). DHTS exhibits a potential anti-proliferative effect in various human cancer cells. However, the mechanisms of action of DHTS as an anti-cancer agent have not been fully elucidated. Therefore, the present study investigated the anti-cancer effect of DHTS in terms of cell cycle regulation and the regulation of the AMP-activated protein kinase (AMPK)/Akt/mTOR signaling pathway in SK-HEP-1 human hepatocellular carcinoma cells.

METHODS:

The anti-proliferative effects of DHTS were evaluated by the sulforhodamine B assay in SK-HEP-1 cells. Cell cycle distribution was analyzed by flow cytometry. The elucidation of mechanisms of action such as the AMPK/AKT/mTOR and mitogen-activated protein kinase (MAPK) pathway was assessed by Western blot analysis.

RESULTS:

DHTS showed a significant anti-proliferative activity against SK-HEP-1 cells. DHTS induced cell cycle arrest in the G0/G1 phase, which was mediated by downregulation of cyclin D1, cyclin A, cyclin E, CDK4, CDK2, c-Myc and p-Rb expression and with increased expression of the CDK inhibitor p21. DHTS also activated the AMPK signaling. In addition, DHTS downregulated the Akt/mTOR and MAPK signaling pathways.

CONCLUSIONS:

Our results suggest that the anti-proliferative activity of DHTS might be associated with the induction of G0/G1 phase cell cycle arrest and regulation of AMPK/Akt/mTOR and MAPK signaling pathways in SK-HEP-1 cells.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Protein Kinases / Down-Regulation / Cell Cycle / Blotting, Western / Cyclins / Carcinoma, Hepatocellular / Cyclin A / Cyclin D1 / Cyclin E / Salvia miltiorrhiza Limits: Humans Language: English Journal: Journal of Cancer Prevention Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Protein Kinases / Down-Regulation / Cell Cycle / Blotting, Western / Cyclins / Carcinoma, Hepatocellular / Cyclin A / Cyclin D1 / Cyclin E / Salvia miltiorrhiza Limits: Humans Language: English Journal: Journal of Cancer Prevention Year: 2018 Type: Article