Apigenin induces apoptosis via tumor necrosis factor receptor- and Bcl-2-mediated pathway and enhances susceptibility of head and neck squamous cell carcinoma to 5-fluorouracil and cisplatin.

Abstract

BACKGROUND:

Apigenin, a natural plant flavone, may have chemopreventive and therapeutic potentials for anti-inflammatory, antioxidant, and anti-cancer. Nevertheless, the anti-tumor effect of apigenin on human head and neck squamous cell carcinoma (HNSCC) is not fully understood.

METHODS:

The antioxidant capacity and protective effects of apigenin against oxidative stress in murine normal embryonic liver BNLCL2 cells are examined. Cell viability, morphologic change, clonogenic survival, cell cycle distribution, reactive oxygen species (ROS) production, glutathione formation, and death receptors- and Bcl-2-mediated caspase pathways of HNSCC SCC25 cells and A431 cells with apigenin are investigated.

RESULTS:

Apigenin inhibits the growth of SCC25 and A431 cells and induces cell cycle arrest in the G2/M phase. Apigenin has an antioxidant capacity as well as the ability to inhibit lipid peroxidation. It protects BNLCL2 cells against oxidative damage, and is potentially able to prevent cancer. Apigenin increases intracellular ROS levels and reduces levels of glutathione; it also induces cell apoptosis via tumor necrosis factor receptor (TNF-R)-, TNF-related apoptosis-inducing ligand receptor (TRAIL-R)-, and Bcl-2-mediated caspase-dependent cell death pathways in SCC25 cells. The combination of apigenin with 5-fluorouracil (5-Fu) or cisplatin induces the dramatic death of SCC25 cells.

CONCLUSIONS:

Apigenin induces SCC25 cell apoptosis via the up-regulation of both TNF-R and TRAIL-R signaling pathways, and has a synergistic effect on the inhibition of cell proliferation in combination with 5-Fu or cisplatin.

GENERAL SIGNIFICANCE:

These analytical findings suggest that apigenin may be a good therapeutic agent against HNSCC cells.

• Authors: Leong-Perng Chan, Tzung-Han Chou, Hsiou-Yu Ding, Pin-Ru Chen, Feng-Yu Chiang, Po-Lin Kuo, Chia-Hua Liang
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1820 Issue 7 Pg. 1081-91 (Jul 2012) ISSN: 0006-3002 [Print] Netherlands
• PMID: 22554915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• Reactive Oxygen Species
• Receptors, Tumor Necrosis Factor
• TNF-Related Apoptosis-Inducing Ligand
• Apigenin
• Caspases
• Cisplatin
• Fluorouracil

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apigenin (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
• Caspases (genetics, metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Cisplatin (administration & dosage)
• Drug Synergism
• Flow Cytometry
• Fluorouracil (administration & dosage)
• Head and Neck Neoplasms (drug therapy, metabolism, pathology)
• Humans
• Lipid Peroxidation (drug effects)
• Liver (cytology, drug effects, metabolism)
• Melanoma (drug therapy, metabolism, pathology)
• Mice
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA, Messenger (genetics)
• Reactive Oxygen Species (metabolism)
• Receptors, Tumor Necrosis Factor (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Skin Neoplasms (drug therapy, metabolism, pathology)
• Squamous Cell Carcinoma of Head and Neck
• TNF-Related Apoptosis-Inducing Ligand (genetics, metabolism)