Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways

Oh,Hana; Yoon,Goo; Shin,Jae-Cheon; Park,Seon-Min; Cho,Seung-Sik; Cho,Jin Hyoung; Lee,Mee-Hyun; Liu,Kangdong; Cho,Young Sik; Chae,Jung-Il; Shim,Jung-Hyun

doi:10.3892/ijo.2016.3365

Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways

Authors:
- Hana Oh
- Goo Yoon
- Jae-Cheon Shin
- Seon-Min Park
- Seung-Sik Cho
- Jin Hyoung Cho
- Mee-Hyun Lee
- Kangdong Liu
- Young Sik Cho
- Jung-Il Chae
- Jung-Hyun Shim
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Affiliations: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea, Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk 790‑834, Republic of Korea, Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 651-756, Republic of Korea, The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan 450001, P.R. China, College of Pharmacy, Keimyung University, Dalseo-gu, Daegu 704-701, Republic of Korea
Published online on: February 1, 2016 https://doi.org/10.3892/ijo.2016.3365
Pages: 1749-1757

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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 upregulation 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.

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