Oridonin induces apoptosis in oral squamous cell carcinoma probably through the generation of reactive oxygen species and the p38/JNK MAPK pathway

Oh,Ha-Na; Seo,Ji-Hye; Lee,Mee-Hyun; Yoon,Goo; Cho,Seung-Sik; Liu,Kangdong; Choi,Hyunji; Oh,Keon Bong; Cho,Young-Sik; Kim,Hangun; Han,A Lum; Chae,Jung-Il; Shim,Jung-Hyun

doi:10.3892/ijo.2018.4319

Oridonin induces apoptosis in oral squamous cell carcinoma probably through the generation of reactive oxygen species and the p38/JNK MAPK pathway

Authors:
- Ha-Na Oh
- Ji-Hye Seo
- Mee-Hyun Lee
- Goo Yoon
- Seung-Sik Cho
- Kangdong Liu
- Hyunji Choi
- Keon Bong Oh
- Young-Sik Cho
- Hangun Kim
- A Lum Han
- 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 58554, Republic of Korea, Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju 54896, Republic of Korea, The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan 450008, P.R. China, Department of Biological Sciences, Dong-A University, Busan 49315, Republic of Korea, Animal Biotechnology Division, National Institute of Animal Science, RDA, Wanju 55365, Republic of Korea, Department of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon 57922, Republic of Korea, Department of Family Medicine, Medical Hospital, Wonkwang University, Iksan, Chonbuk 54538, Republic of Korea
Published online on: March 16, 2018 https://doi.org/10.3892/ijo.2018.4319
Pages: 1749-1759

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Abstract

The anti-inflammatory effects of oridonin (Ordn) have been well established in previous studies. However, the apoptotic effects of Ordn on oral cancer cells have not yet been evaluated, at least to the best of our knowledge. The aim of this study was to examine the apoptotic activity of Ordn in oral squamous cell carcinoma cells and to eluciudate the underlying mechanisms. For this purpose, we employed experimental techniques, such as MTT assay, DAPI staining, soft agar assay, flow cytometry and western blot analysis. Our results revealed that Ordn suppressed oral cancer cell proliferation and soft agar colony formation, while it induced reactive oxygen species (ROS)-dependent apoptosis in a dose or time-dependent manner. The generation of ROS was detected in HN22 and HSC4 cells treated with Ordn and the use of the free radical scavenger, N-acetyl-L-cysteine, almost blocked Ordn-induced apoptosis. The phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) was manifested in the Ordn-treated cells. Furthermore, Ordn induced the apoptosis of oral cancer cells through the mitochondrial-dependent pathway, involving the loss of mitochondrial membrane potential, the release of cytochrome c, the induction of poly(ADP-Ribose) polymerase (PARP) cleavage, alterations in the ratios of apoptotic proteins and the activation of the caspase cascade. Taken together, these findings indicate that Ordn induces the apoptosis of oral cancer cells probably via ROS-mediated JNK/p38 MAPK and mitochondrial pathways; thus, Ordn may have potential for use in the treatment of oral cancer.

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