Licochalcone-E induces caspase-dependent death of human pharyngeal squamous carcinoma cells through the extrinsic and intrinsic apoptotic signaling pathways

Yu,Sang‑Joun; Cho,In‑A; Kang,Kyeong‑Rok; Jung,Yi‑Ra; Cho,Seung  Sik; Yoon,Goo; Oh,Ji‑Su; You,Jae‑Seek; Seo,Yo‑Seob; Lee,Gyeong‑Je; Lee,Sook‑Young; Kim,Do  Kyung; Kim,Chun  Sung; Kim,Su‑Gwan; Jeong,Mi‑Ae; Kim,Jae‑Sung

doi:10.3892/ol.2017.5865

Licochalcone-E induces caspase-dependent death of human pharyngeal squamous carcinoma cells through the extrinsic and intrinsic apoptotic signaling pathways

Authors:
- Sang‑Joun Yu
- In‑A Cho
- Kyeong‑Rok Kang
- Yi‑Ra Jung
- Seung Sik Cho
- Goo Yoon
- Ji‑Su Oh
- Jae‑Seek You
- Yo‑Seob Seo
- Gyeong‑Je Lee
- Sook‑Young Lee
- Do Kyung Kim
- Chun Sung Kim
- Su‑Gwan Kim
- Mi‑Ae Jeong
- Jae‑Sung Kim
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Affiliations: Department of Periodontology, School of Dentistry, Chosun University, Gwangju 501‑759, Republic of Korea, Department of Biodental Engineering, Graduate School, Chosun University, Gwangju 501‑759, Republic of Korea, Regional Innovation Center for Dental Science and Engineering, Chosun University, Gwangju 501‑759, Republic of Korea, Department of Pharmacy, College of Pharmacy, Mokpo National University, Mokpo, Jeollanamdo 353‑729, Republic of Korea, Department of Oral and Maxillofacial Surgery, Chosun University, Gwangju 501‑759, Republic of Korea, Department of Oral and Maxillofacial Radiology, Chosun University, Gwangju 501‑759, Republic of Korea, Department of Prosthodontics, Chosun University, Gwangju 501‑759, Republic of Korea, Oral Biology Research Institute, Chosun University, Gwangju 501‑759, Republic of Korea, Department of Dental Hygiene, Kangwon National University, Samcheok, Gangwon 259‑13, Republic of Korea, Pre‑Dentistry, School of Dentistry, Chosun University, Gwangju 501‑759, Republic of Korea
Published online on: March 16, 2017 https://doi.org/10.3892/ol.2017.5865
Pages: 3662-3668

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Abstract

The aim of the present study was to investigate licochalcone-E (Lico-E)-induced apoptosis and the associated apoptotic signaling pathway in FaDu cells, a human pharyngeal squamous carcinoma cell line. Treatment with Lico‑E exhibited significant cytotoxicity on FaDu cells in a concentration‑dependent manner. The IC50 value of Lico-E in FaDu cells was ~50 µM. Treatment with Lico‑E increased the number of dead FaDu cells. Furthermore, chromatin condensation, which is associated with apoptotic cell death, was observed in FaDu cells treated with Lico‑E for 24 h. By contrast, Lico‑E did not produce cytotoxicity or increase the number of dead cells when applied to human normal oral keratinocytes (hNOKs). Furthermore, chromatin condensation was not observed in hNOKs treated with Lico‑E. Treatment with Lico‑E increased the expression of Fas ligand and the cleaved form of caspase‑8 in FaDu cells. Furthermore, treatment with Lico‑E increased the expression of pro‑apoptotic factors, including apoptosis regulator BAX, Bcl‑2‑associated agonist of cell death, apoptotic protease‑activating factor 1, caspase‑9 and tumor suppressor p53, while decreasing the expression of anti‑apoptotic factors, including apoptosis regulator Bcl‑2 and Bcl‑2‑like protein 1 in FaDu cells. The expression of cleaved caspases‑3 and poly (ADP‑ribose) polymerase was significantly upregulated following treatment with Lico‑E in FaDu cells, while Lico‑E‑induced apoptotic FaDu cell death was partially suppressed by treatment with Z‑VAD‑FMK, a pan caspase inhibitor. Therefore, Lico‑E‑induced oral cancer (OC) cell‑specific apoptosis is mediated by the death receptor-dependent extrinsic and mitochondrial‑dependent intrinsic apoptotic signaling pathways. In conclusion, these data suggested that Lico‑E exhibits potential chemopreventive effects and warrants further developed as a chemotherapeutic agent against OC.

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