Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells

• Published in: Nutrients 2019-01, Vol.11 (2), p.263
• Main Authors: Sang Eun, Ha, Seong Min, Kim, Ho Jeong, Lee, Vetrivel, Preethi, Venkatarame Gowda Saralamma, Venu, Jeong Doo, Heo, Eun Hee, Kim, Sang Joon, Lee, Gon Sup, Kim
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; Apigenin - pharmacology; Apoptosis; Apoptosis - drug effects; Biocompatibility; Cancer therapies; Caspase-3; Caspase-8; Cell cycle; cell cycle arrest; Cell Cycle Checkpoints - drug effects; Cell death; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Cyclin-dependent kinases; Cytochrome; DNA Fragmentation - drug effects; fas Receptor - metabolism; FasL protein; flavonoid; Flavonoids; Gastric cancer; Hepatocellular carcinoma; Humans; Immunoglobulins; In vivo methods and tests; Kinases; Liver cancer; Liver Neoplasms - metabolism; Mitochondria; Morphology; Poly(ADP-ribose) polymerase; scutellarein; Toxicity; Toxicology; Viability
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu11020263

Scutellarein (SCU), a flavone found in the perennial herb , is known for a wide range of biological activities. In the present study, we investigated the effects of treatment with SCU flavonoids on inducing apoptosis via the extrinsic pathway in Hep3B cells. SCU treatment significantly inhibited Hep3B cell proliferation and induced G2/M phase cell cycle arrest by inhibiting the expression levels of the proteins Cdc25C, cdk1 and Cyclin B1. Allophycocyanin (APC)/Annexin V and propidium iodide (PI) double-staining showed upregulation of apoptotic cell death fraction. We further confirmed apoptosis by 4'-6-diamidino-2-phenylindole (DAPI) fluorescent staining and observed DNA fragmentation with agarose gel electrophoresis. Further, immunoblotting results showed that treatment with SCU showed no changes in Bax and Bcl-xL protein levels. In addition, SCU treatment did not affect the mitochondrial membrane potential in Hep3B cells. On the contrary, treatment with SCU increased the expression of Fas and Fas ligand (FasL), which activated cleaved caspase-8, caspase-3, and polymeric adenosine diphosphate ribose (PARP), whereas the expression level of death receptor 4 (DR4) decreased. We confirmed that the proteins expressed upon treatment with SCU were involved in the Fas-mediated pathway of apoptosis in Hep3B cells. Thus, our findings in the current study strongly imply that SCU can be a basic natural source for developing potent anti-cancer agents for hepatocellular carcinoma (HCC) treatment.