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J Cell Physiol. 2019 Feb;234(2):1780-1793. doi: 10.1002/jcp.27050. Epub 2018 Aug 2.

Licochalcone D directly targets JAK2 to induced apoptosis in human oral squamous cell carcinoma.

Author information

1
Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju, Republic of Korea.
2
Department of Animal Science, Chonbuk National University, Jeonju, Republic of Korea.
3
Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan County, Republic of Korea.
4
China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China.
5
College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
6
Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk, Republic of Korea.
7
Department of Pharmacy, Keimyung University, Daegu, Republic of Korea.

Abstract

Licochalcone (LC) families have been reported to have a wide range of biological function such as antioxidant, antibacterial, antiviral, and anticancer effects. Although various beneficial effects of LCD were revealed, its anticancer effect in human oral squamous cancer has not been identified. To examine the signaling pathway of LCD's anticancer effect, we determined whether LCD has physical interaction with Janus kinase (JAK2)/signal transducer and activator of transcription-3 (STAT3) signaling, which is critical in promoting cancer cell survival and proliferation. Our results demonstrated that LCD inhibited the kinase activity of JAK2, soft agar colony formation, and the proliferation of HN22 and HSC4 cells. LCD also induced mitochondrial apoptotic events such as altered mitochondrial membrane potential and reactive oxygen species production. LCD increased the expression of apoptosis-associated proteins in oral squamous cell carcinoma (OSCC) cells. Finally, the xenograft study showed that LCD significantly inhibited HN22 tumor growth. Immunohistochemical data supported that LCD suppressed p-JAK2 and p-STAT3 expression and induced cleaved-caspase-3 expression. These results indicate that the anticancer effect of LCD is due to the direct targeting of JAK2 kinase. Therefore, LCD can be used for therapeutic application against OSCC.

KEYWORDS:

JAK2; STAT3; apoptosis; licochalcone (LC) D; mitochondrial membrane potential (MMP); oral squamous cell carcinoma (OSCC); reactive oxygen species (ROS)

PMID:
30070696
DOI:
10.1002/jcp.27050

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