Journal
ARCHIVES OF ORAL BIOLOGY
Volume 60, Issue 9, Pages 1283-1298Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.archoralbio.2015.05.009
Keywords
Acacetin; Apoptosis; Mitochondrial pathway; Caspases; MAPKs signal pathway; Cell cycles; Oral cancer
Categories
Funding
- National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [KRF-2009-0094027]
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Background: Acacetin (5,7-dihydroxy-40-methoxyflavone), present in safflower seeds, plants, flowers, Cirisium rhinoceros Nakai, has been reported to be able to exert antiperoxidative, 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 25 mu g/mL over 24 h 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 100 mu g/mL of acacetin for 24 h. 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. (C) 2015 Elsevier Ltd. All rights reserved.
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