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

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.

• Authors: Ji-Hye Seo, Hyun Woo Choi, Ha-Na Oh, Mee-Hyun Lee, Eunae Kim, Goo Yoon, Seung-Sik Cho, Seon-Min Park, Young Sik Cho, Jung-Il Chae, Jung-Hyun Shim
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 2 Pg. 1780-1793 (02 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30070696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents, Phytogenic
• Chalcones
• Janus Kinase Inhibitors
• licochalcone D
• JAK2 protein, human
• Janus Kinase 2

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chalcones (pharmacology)
• Humans
• Janus Kinase 2 (antagonists & inhibitors, metabolism)
• Janus Kinase Inhibitors (pharmacology)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Mitochondria (drug effects, metabolism, pathology)
• Molecular Targeted Therapy
• Mouth Neoplasms (drug therapy, enzymology, pathology)
• Signal Transduction
• Squamous Cell Carcinoma of Head and Neck (drug therapy, enzymology, pathology)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays