Emodin mitigates the oxidative stress induced by cisplatin in osteosarcoma MG63 cells.
Previously, the application of cisplatin in chemotherapy was limited due to the significant side effects on normal cell growth. In the present study, the concomitant application of emodin with cisplatin was demonstrated to ameliorate cisplatin-induced oxidative stress and markedly suppress tumor cell proliferation for the first time. Human osteosarcoma MG-63 cells were treated with cisplatin alone or in combination with emodin. The cell viability was determined by MTS assays and the augmentation of reactive oxygen species were determined by fluorogenic probes; in addition, a stable MG-63 subline bearing antioxidant response element (ARE)-driven luciferase expression was developed to monitor the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-ARE signaling pathway. The results indicated that cisplatin or emodin may inhibit MG-63 cell proliferation in a time- or dose-dependent manner, respectively. Concomitant treatment with cisplatin and emodin demonstrated synergic anti-tumor effects. Cisplatin augmented reactive oxygen species in the MG-63 cells, followed by the translocation of Nrf2 from the cytoplasm into the nucleus, which triggered ARE-driven luciferase expression. The addition of emodin diminished the previously described phenomenon, resulting in decreased ROS augmentation, translocation of Nrf2 and ARE-driven luciferase activity. In conclusion, emodin could ameliorate cisplatin-induced oxidative stress and protect the cells from oxidative stress-induced damage. The findings of the present study provide a novel strategy for the treatment of osteosarcoma using emodin and cisplatin.
Department of Reparative and Reconstructive Surgery of Orthopedics, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Li
L
Yan
Department of Reparative and Reconstructive Surgery of Orthopedics, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Rui
R
Hu
Department of Reparative and Reconstructive Surgery of Orthopedics, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Song
S
Tu
Department of Reparative and Reconstructive Surgery of Orthopedics, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Wen-Jun
WJ
Cheng
Department of Reparative and Reconstructive Surgery of Orthopedics, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Qiong
Q
Zheng
Department of Reparative and Reconstructive Surgery of Orthopedics, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Jun-Wen
JW
Wang
Department of Reparative and Reconstructive Surgery of Orthopedics, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Wu-Sheng
WS
Kan
Department of Reparative and Reconstructive Surgery of Orthopedics, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China.
Yi-Jun
YJ
Ren
cisplatin; emodin; osteosarcomas; oxidative stress