title: Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways.
abstract: Licochalcone B (Lico B), which belongs to the retrochalcone family, is isolated from the roots of Chinese licorice. Lico B has been reported to have several other useful pharmacological properties, such as anti-inflammatory, antibacterial, antioxidant, antiulcer, anticancer, and anti-metastasis activities. We elucidated the underlying mechanism by which Lico B can induce apoptosis in oral squamous cell carcinoma (OSCC). Our results showed that exposure of OSCC cells (HN22 and HSC4) to Lico B significantly inhibited cell proliferation in a time- and concentration-dependent manner. Lico B caused cell cycle arrest at G1 phase along with downregulation of cyclin D1 and upregulation of p21 and p27 proteins. Lico B also facilitated the diffusion of phospholipid phosphatidylserine (PS) from inner to outer leaflets of the plasma membrane with chromatin condensation, DNA fragmentation, accumulated sub-G1 population in a concentration-dependent manner. Moreover, Lico B promoted the generation of reactive oxygen species (ROS), which, in turn, can induce CHOP, death receptor (DR) 4 and DR5. Lico B treatment induced downregulation of anti-apoptotic proteins (Bid and Bcl-xl and Mcl-1), and up-regulation of pro-apoptotic protein (Bax). Lico B also led to the loss of mitochondrial membrane potential (MMP), resulting in cytochrome c release. As can be expected from the above results, the apoptotic protease activating factor-1 (Apaf-1) and survivin were oppositely expressed in favor of apoptotic cell death. This notion was supported by the fact that Lico B activated multi-caspases with cleavage of poly (ADP-ribose) polymerase (PARP) protein. Therefore, it is suggested that Lico B is a promising drug for the treatment of human oral cancer via the induction of apoptotic cell death.
authors: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors: Hana
authors: H
authors: Oh
authors: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors: Goo
authors: G
authors: Yoon
authors: Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea.
authors: Jae-Cheon
authors: JC
authors: Shin
authors: Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea.
authors: Seon-Min
authors: SM
authors: Park
authors: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors: Seung-Sik
authors: SS
authors: Cho
authors: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 651-756, Republic of Korea.
authors: Jin Hyoung
authors: JH
authors: Cho
authors: The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan 450001, P.R. China.
authors: Mee-Hyun
authors: MH
authors: Lee
authors: The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan 450001, P.R. China.
authors: Kangdong
authors: K
authors: Liu
authors: College of Pharmacy, Keimyung University, Dalseo-gu, Daegu 704-701, Republic of Korea.
authors: Young Sik
authors: YS
authors: Cho
authors: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 651-756, Republic of Korea.
authors: Jung-Il
authors: JI
authors: Chae
authors: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors: Jung-Hyun
authors: JH
authors: Shim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; D010718:Phosphatidylserines; C541528:licochalcone B