Cordycepin Induces Apoptosis through JNK-Mediated Caspase Activation in Human OEC-M1 Oral Cancer Cells

Kuo-Lung Tung; Su-Zhen Wu; Chun-Chuan Yang; Hong-Yi Chang; Chun-Sheng Chang; Yan-Hsiung Wang; Bu-Miin Huang; Yu-Yan Lan

doi:10.1155/2022/1842363

Cordycepin Induces Apoptosis through JNK-Mediated Caspase Activation in Human OEC-M1 Oral Cancer Cells

Evid Based Complement Alternat Med. 2022 Oct 3:2022:1842363. doi: 10.1155/2022/1842363. eCollection 2022.

Authors

Kuo-Lung Tung^{1

2}, Su-Zhen Wu^{3

4}, Chun-Chuan Yang⁵, Hong-Yi Chang⁶, Chun-Sheng Chang⁶, Yan-Hsiung Wang^{2

7

8

9}, Bu-Miin Huang^{10

11}, Yu-Yan Lan¹²

Affiliations

¹ Department of Oral Hygiene, Shu-Zen Junior College of Medicine and Management, Kaohsiung 82144, Taiwan.
² School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
³ Department of Anesthesia, Chi-Mei Medical Center, Liouying, Tainan 73657, Taiwan.
⁴ Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan 73658, Taiwan.
⁵ Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung 82144, Taiwan.
⁶ Department of Biotechnology and Food Technology, College of Engineering, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan.
⁷ Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁸ Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁹ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
¹⁰ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
¹¹ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
¹² School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan.

Abstract

Cordycepin, a bioactive compound extracted from Cordyceps sinensis, can induce apoptosis in human OEC-M1 oral cancer cells. However, the exact mechanism is still unclear. The present study aimed to investigate the underlying mechanism of cordycepin-induced apoptosis in OEC-M1 cells. Following treatment with cordycepin, apoptosis was examined and quantified using a DNA laddering assay and a cytokeratin 18 fragment enzyme-linked immunosorbent assay, respectively. Expressions of mitogen-activated protein kinases (MAPKs) and apoptosis-related proteins were detected by the western blot analysis. Our results show that a pan-caspase inhibitor, Z-VAD-FMK, could significantly inhibit cordycepin-induced apoptosis in OEC-M1 cells. In addition, treatment with cordycepin not only activated caspase-8, caspase-9, and caspase-3 but also induced Bid and poly ADP-ribose polymerase cleavages. Furthermore, cordycepin also induced the activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase, and p38 MAPKs. Among MAPKs, activation of JNK solely contributed to cordycepin-induced apoptosis with the activation of caspase-8, caspase-9, and caspase-3 and cleavage of PARP. Taken together, the present study demonstrated that cordycepin activated JNK and caspase pathways to induce apoptosis in OEC-M1 cells.