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

Abstract

Scutellarein (SCU), a flavone found in the perennial herb Scutellaria baicalensis, 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.

Natural Dietary Supplement, Carvacrol, Alleviates LPS-Induced Oxidative Stress, Neurodegeneration, and Depressive-Like Behaviors via the Nrf2/HO-1 Pathway

“…68 Likewise, a close interplay of caspase-3 and JNK is implicated in the execution of the mitochondrial apoptotic pathway in several neurodegenerative disorders. 69,70 Our data demonstrated a considerably decreased expression of anti-apoptotic Bcl2 as well as a significant increase in the expression of JNK and caspase-3 in LPS-injected rats. Carvacrol exhibited a substantial reduction in LPS-provoked elevation of pro-apoptotic proteins and p-JNK associated with increased anti-apoptotic mediators.…”

Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling

“…Inflammatory mediators, UV radiation, and oxidative stress trigger the JNK cascades [63]. Similarly, the anti- and pro-apoptotic protein markers Bcl-2 and Bax play an important role in the regulation of apoptotic cell death pathways at the mitochondrial level [64,65]. Another factor responsible for apoptotic neurodegeneration is the caspase cascade, especially Caspase-3, a principal effector in apoptotic cascades resulting in neurodegeneration [66].…”

<p>Transcriptomics Analysis of the Tumor-Inhibitory Pathways of 6-Thioguanine in MCF-7 Cells via Silencing DNMT1 Activity</p>

“…With the activation of FAS, FAS ligand (FasL) was also up-regulated, thus triggering the exogenous apoptosis pathway, as described in the report about the effect of scutellarein on Hep3B cells. 27 In addition, previous research has shown that in NIH 3T3 cells, DNMT1 regulates the CpG methylation of the FAS promotor to regulate the mRNA expression level of FAS. 28 Fas and FasL, which induced cell apoptosis, were activated in a report related to the effect of lycorine hydrochloride on MCF-7 cells.…”