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The mechanism of acacetin-induced apoptosis on oral squamous cell carcinoma

Authors
 Chae-Doo Kim  ;  Jeong-Dan Cha  ;  ShengJin Li  ;  In-Ho Cha 
Citation
 ARCHIVES OF ORAL BIOLOGY, Vol.60(9) : 1283-1298, 2015 
Journal Title
 ARCHIVES OF ORAL BIOLOGY 
ISSN
 0003-9969 
Issue Date
2015
MeSH
Apoptosis/drug effects* ; Blotting, Western ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Squamous Cell/enzymology ; Caspase 3/metabolism ; Caspase 8/metabolism ; Caspase 9/metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Survival/drug effects ; Cytochromes c/metabolism ; DNA Fragmentation ; Flavones/pharmacology* ; Flow Cytometry ; Humans ; In Situ Nick-End Labeling ; Membrane Potential, Mitochondrial/drug effects ; Mitogen-Activated Protein Kinases/metabolism ; Mouth Neoplasms/drug therapy* ; Mouth Neoplasms/enzymology ; Oligopeptides/pharmacology ; Poly(ADP-ribose) Polymerases/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Signal Transduction
Keywords
Acacetin ; Apoptosis ; Caspases ; Cell cycles ; MAPKs signal pathway ; Mitochondrial pathway ; Oral cancer
Abstract
BACKGROUND: Acacetin (5,7-dihydroxy-40-methoxyflavone), present in safflower seeds, plants, flowers, Cirisium rhinoceros Nakai, has been reported to be able to exert anti-peroxidative, anti-inflammatory, anti-plasmodial, and anti-proliferative activities by inducing apoptosis and blocking the progression of cell cycles. OBJECTIVE AND DESIGN: The objective of this study is to investigate the mechanism of acacetin-induced apoptosis of oral squamous cell carcinoma cell line (HSC-3). RESULTS: Acacetin caused 50% growth inhibition (IC50) of HSC-3 cells at 25μg/mL over 24h in the MTT assay. Apoptosis was characterized by DNA fragmentation and increase of sub-G1 cells and involved activation of caspase-3 and PARP (poly-ADP-ribose polymerase). Maximum caspase-3 activity was observed with 100μg/mL of acacetin for 24h. Caspase-8 and -9 activation cascades mediated the activation of caspase-3. Acacetin caused reduction of Bcl-2 expression leading to an increase of the Bax:Bcl-2 ratio. It also caused a loss of mitochondrial membrane potential that induced release of cytochrome c into the cytoplasm. Pretreatment with casapse-3 (Z-DEVD-FMK), -8 (Z-IETD-FMK), and 9 inhibitor (z-LEHD-fmk) inhibited the acacetin-induced loss of mitochondrial membrane potential and release of cytochrome c. The mitogen-activated protein kinases (MAPKs) were activated by acacetin. Moreover, pretreating the cells with each of the caspase inhibitor or MAPKs specific inhibitors apparently inhibited acacetin-induced cytotoxicity of HSC-3 cells. CONCLUSION: In conclusion, acacetin induce the apoptosis of oral squamous cell carcinoma cell line, which is closely related to its ability to activate the MAPK-mediated signaling pathways with the subsequent induction of a mitochondria- and caspase-dependent mechanism. These results strongly suggest that acacetin might have cancer inhibition and therapeutic potential.
Full Text
https://www.sciencedirect.com/science/article/pii/S0003996915001326
DOI
10.1016/j.archoralbio.2015.05.009
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
Yonsei Authors
Cha, In Ho(차인호) ORCID logo https://orcid.org/0000-0001-8259-2190
Cha, Jeong Dan(차정단)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/157003
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