title: Licochalcone A induces apoptosis in KB human oral cancer cells via a caspase-dependent FasL signaling pathway.
abstract: Licochalcone A (Lico-A) is a natural phenol licorice compound with multiple bioactivities, including anti-inflammatory, anti-microbial, anti-fungal and osteogenesis-inducing properties. In the present study, we investigated the Lico-A-induced apoptotic effects and examined the associated apoptosis pathway in KB human oral cancer cells. Lico-A decreased the number of viable KB oral cancer cells. However, Lico-A did not have an effect on primary normal human oral keratinocytes. In addition, the IC50 value of Lico-A was determined to be ~50 µM following dose-dependent stimulation. KB oral cancer cells stimulated with Lico-A for 24 h showed chromatin condensation by DAPI staining, genomic DNA fragmentation by agarose gel electrophoresis and a gradually increased apoptotic cell population by FACS analysis. These data suggest that Lico-A induces apoptosis in KB oral cancer cells. Additionally, Lico‑A‑induced apoptosis in KB oral cancer cells was mediated by the expression of factor associated suicide ligand (FasL) and activated caspase-8 and -3 and poly(ADP-ribose) polymerase (PARP). Furthermore, in the KB oral cancer cells co-stimulation with a caspase inhibitor (Z-VAD-fmk) and Lico-A significantly abolished the apoptotic phenomena. Our findings demonstrated that Lico‑A-induced apoptosis in KB oral cancer cells involves the extrinsic apoptotic signaling pathway, which involves a caspase-dependent FasL-mediated death receptor pathway. Our data suggest that Lico-A be developed as a chemotherapeutic agent for the management of oral cancer.
authors: Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Jae-Sung
authors: JS
authors: Kim
authors: Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Mi-Ra
authors: MR
authors: Park
authors: Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Sook-Young
authors: SY
authors: Lee
authors: Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Do Kyoung
authors: DK
authors: Kim
authors: Department of Oral Biochemistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Sung-Min
authors: SM
authors: Moon
authors: Department of Oral Biochemistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Chun Sung
authors: CS
authors: Kim
authors: Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729, Republic of Korea.
authors: Seung Sik
authors: SS
authors: Cho
authors: Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729, Republic of Korea.
authors: Goo
authors: G
authors: Yoon
authors: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
authors: Hee-Jeong
authors: HJ
authors: Im
authors: Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Jae-Seek
authors: JS
authors: You
authors: Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Ji-Su
authors: JS
authors: Oh
authors: Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Su-Gwan
authors: SG
authors: Kim
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics; D053181:Caspase 8 / Q000235:genetics; D061945:Caspase Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D002843:Chromatin / Q000187:drug effects / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D053222:Fas Ligand Protein / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007624:KB Cells; D015603:Keratinocytes / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D047188:Chalcones; D002843:Chromatin; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005419:Flavonoids; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053181:Caspase 8; C070840:licochalcone A; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one